After reading "How to Use an Article About Genetic Association C: What Are the Results and Will They Help Me
in
Caring for My Patients?" by Attia et al. and "The Positives, Protocols,
and Perils of Genome-Wide Association" by Purcell and Neale, briefly
describe the strengths, limitations, and future applications of Genetic
Association studies?
Choose one of the four following activities and share your response in the "Comment Section below":
1. You can share the new, 'surprising' information you learned
2. Ask a question that needs additional clarification,
3. Share a news link relevant to the discussion.
4. Reply to another student's comment.
One point that stuck out to me after reading "How to Use an Article About Genetic Association C: What Are the Results and Will They Help Me in Caring for My Patients?" by Attia et al. is something to keep in mind when looking at genetic tests is that certain diseases are more or less common in certain ethnic groups. An example of this is BRCA 1 and BRCA 2 mutations in Ashkenazi Jews. Ashkenazi Jews are originally from central or eastern Europe, and historically lived in a geographically isolated population. Genetic traits of the population were passed down through generations, including a greater frequency of BRCA 1 and BRCA 2 mutations. These mutations increase risk for breast, ovarian, and prostate cancer. In the general population, only about 1/800 people have a mutation involving BRCA 1 or BRCA 2 genes, but in Ashkenazi Jews, about 1/40 people have this mutation. An important thing to remember about genetic testing is that not everyone who carries the gene will develop cancer.
ReplyDeleteSource:
https://www.fhcrc.org/en/events/cancer-in-our-communities/ashkenazi-jewish-communities.html
What has really stuck out to me after reading these articles is the future implications of genetic testing and genetic association studies, particularly when it comes to training and staffing healthcare professionals. Especially with the availability of DTC Genetic Testing, patients will turn to physicians to interpret their genetic information and determine risk. In time as the popularity and awareness of these tests increase, physicians must be able to correctly present and discuss genetic risk with their patients. My proposition is that interpretation of genetic code should fall solely in the hands of genetic counselors and I would suggest that we employ more genetic counselors in upcoming years. Physicians should be trained and have the authority to order genetic testing for patients who have the disease in their family or have a particularly high risk.
ReplyDeleteIn response to Anika's question, I think that in working with genetic information, there is often query about how much is too much, and/or how far scientists and physicians will go with the information. I took a medical ethics course last year that spent a bit of time investigating whether parents expecting children should be able to determine information genetically about the children and consequently pick and choose the "best genes" and create a "designer" baby. Critics mostly thought that genetic testing about an embryo should only lead to decision making in cases where it is found out the embryo has a harmful disease that would greatly limit quality of life. I agree that this is something great about prenatal testing; a parent can find out if a child has genetic disorder very early and prepare and make decisions accordingly. More critics of this genetic selection through in vitro fertilization or some other method criticized it because they thought parents would become extremist and insist on inserting genes for blue eyes and blonde hair and the like, and genetic variation would be lost. I don't think this will happen just yet, but as for changing the human genome at our will and eliminating certain diseases as Anika mentioned, I am wondering if this can already be done today in the form of gene therapy that we talked about last week. With gene therapy, we are not able to eliminate disease just yet, but progression can be slowed or halted as our individual genome is changed.
ReplyDeleteExpanding upon your discussion of genetic selection through in vitro fertilization, I found this interesting article pertaining to something similar. In class, Professor Chan said that the opposite of gene therapy were preventative strategies such as vaccinations. In the article I provided below, I found researchers who had managed to find a way to correct mutations on the mitochondrial DNA passed on through a woman's egg. These researchers would simply remove the faulty portion of the mitochondrial DNA and replace it with healthy genes from another woman's egg. By doing this, they hoped to prevent the occurrence of disorders resulting from the mutations of these few, though important, genes. Although there are many shortcomings with this research, including ethical problems as well as the potential for new genetic disorders, I think this type of research is very interesting and I cannot help but wonder how we will try to expand upon this for the future (assuming that they are ever allowed to try this on humans).
DeleteSource: http://www.npr.org/blogs/health/2012/10/24/163509093/geneticists-breach-ethical-taboo-by-changing-genes-across-generations
After reading both articles, my thoughts about the importance of GWAS are confirmed. In today's age of increasing technology, GWAS and DTC genetic testing are becoming the norm. I think that it is very interesting to see that GWAS are being done to see any genetic links with psychiatric disorders. Since psychiatric disorders are difficult to treat through counseling and medications, it'd be interesting to see a genetic solution come from a GWAS. Especially in today's society, where mental illness has been a hot topic, it'd be an interesting approach to an ever-growing problem. This idea emphasizes the importance of comparing our genes and trying to understand the human genome. We have been talking about gene therapy in class, it'd be a great tool to use if it were possible for depression and anxiety problems. Personally, I feel like the pharmaceutical industry is making a lot of money off of marketing towards depression and anxiety, so finding a genetic basis for these mental illnesses could help psychiatrists and those in the field better understand what can be done to prevent and lessen symptoms from various illnesses.
ReplyDeleteIn response to both Anika and Stefanie's comments, it is an interesting thought to think about controlling for disease at conception, possibly ridding the zygote of it, and possibly the world. I have also taken several medical ethics courses that discussed the idea of "designer babies," and my thoughts have always remained the same. At one point, we might be able to fix the genome, take away a cancer gene at conception. But where is the line drawn? Could we also fix genes that call for poor eyesight? And then does that lead to hair color? The subject gets difficulty and the line blurs. I think that this is a problem that we as a society will have to deal with in the next 50 years or so. GWAS and DTC genetic testing are the first steps. But another problem, that one of the articles mentioned, is that the public doesn't have a basis of genetic knowledge. This could make interpreting results and studies very difficult. As we move into the future, we also must, as health professionals, prepare the public and our patients. This could be done by teaching genomics in high school health classes, or by requiring short online genomics classes for those using DTC products. Either way, something needs to be done to educate the problem, so they know what they will be dealing with.
After reading both articles, I can see there might be some great potential in the future with GWAS. With further knowledge, technology, and research GWAS may improve prevention and treatment methods. However, I believe that we have a long ways to go before this occurs. Joseph Terwilliger, the statistical geneticist Anika was talking had some interesting points. Here’s the critique he made about GWAS back in 2008: http://www.homolog.us/blogs/blog/2013/12/12/rise-fall-human-genetics-common-variant-common-disease-hypothesis/
ReplyDeleteHe criticizes how researchers of GWAS talk about all the success in the studies, but in reality, there have been no successful results. One major limitation of GWAS is that most of the SNP variants found so far by GWAS are associated with only a small increased risk of the disease. This limitation could mean that the hypothesis that most of the genetic risk for complex diseases is due to a disease loci associated with a common variant is wrong. Consequently, all the results so far are not very useful as researchers hoped they would be. I understand where critics of GWAS such as Terwilliger are coming from and have been thinking ‘where are all these promising results?’ Yet, I won’t go as far and say GWAS is a waste of money. As stated above, I think that there is potential for GWAS to be beneficial in the future. Additionally, science is all about discovery and expanding your knowledge and GWAS have accomplished that goal by enhancing understanding of the various genetic loci and pathways associated with a particular disease.
This article: http://ac.els-cdn.com/S0002929711005337/1-s2.0-S0002929711005337-main.pdf?_tid=163d28d0-93b3-11e3-8909-00000aab0f6b&acdnat=1392188493_4ea7378e73c5f7e8b7f6d3e04d410604
tries to refute all the critics against GWAS.
Genome Wide Association Studies (GWAS) appear to have great potential despite many limitations. By identifying genetic variations among people’s genomes and linking these variants with specific traits and diseases, we could much better understand the causes of disease. By identifying disease etiologies through these studies, there is hope for treatments, prevention, and potentially, eradication of certain diseases.
ReplyDeleteDespite this, there any many limitations and issues with GWAS. This relatively new approach requires a very large sample size to correctly determine an association between the SNP and a disease. This vast amount of data from these studies is hard to manage, even with sophisticated software. There appear to be many uncertainties and a high chance of making incorrect associations, possibly due to confounders. What I find most concerning is that while it is necessary and important to identify the disease genes, there may not yet be treatments available for such diseases; therefore, identifying the problem gene may be futile if we don’t have a way to treat or prevent the disease from this information.
All things considered, this new approach is promising and should continue to be studied. New technology allowing for data-sharing will help validate findings, due to the large amount of information from many different sources. Hopefully, this will lead to better understanding of diseases such as ADHD and autism, which are currently being studied.
The article, “Is big data already outpacing health IT?,” brings up an important logistical issue in genomic studies which require vast amounts of data. It explains that despite the benefits and potential of genomic cancer studies, we simply do not have the technology to store or secure the incomprehensible amount of data. Even the newest, most cutting edge computers could take weeks to analyze one tumor, according to Joe Gray from the Knight Cancer Institute at Oregon Health & Science University. Therefore, if we want to be able to make of data, we’re going to first have to address the lagging technology.
Source:
http://www.govhealthit.com/news/big-data-already-outpacing-health-it
After reading these articles and discussing genetic testing in class, it is apparent that genetic testing will become an important component of medicine in the future. The human genome has the ability to tell us a lot about ourselves, but we also don't fully know how to interpret it. There is a lot to learn about these markers and "risk-alleles" before we can truly use them to diagnose illness.
ReplyDeleteThe risk of DTC testing is that people who decide to get their full genome tested may not truly understand what their results mean. Having a certain gene, like BRCA1, does not guarantee that you will develop breast cancer. People who do not understand genomics may not realize how much their lifestyle and behaviors can affect the expression of certain genes, and may panic and seek medical attention when not necessary.
A strength of genetic association studies is offering people a chance to understand their genes and what they are genetically predispositioned to. For instance, if someone had a genetic susceptibility to diabetes, proper adjustments would be exercised to avoid provoking diabetes from occurring. However, this leads to one of the limitations of genetic associations: the possibility of unnecessary paranoia. For example, if someone took a screening test for breast cancer and it came out as positive, there are mental and psychological risks if it was actually a false positive. One would alter their lifestyle for this, and this might even induce stress. One could take it a step further and carry out drastic actions without consulting their doctor. With the proper guidance from certified counselors to explain their results, people can be put at ease, but the paranoia will still be in their minds. I believe genetic association studies is great step forward in understanding genes and applying it to the population, but more needs to be understood before having it available to the general public.
ReplyDeleteGenetic Association studies seem to have a promising future. It is great for preventative care as it allows us to know our risk for certain diseases, which allows us to develop preventative methods as needed, such as preventing heart disease or diabetes with a better diet and exercise. With constantly improving technology I believe GWAS will improve prevention and treatment, however there are always limitations.
ReplyDeleteLimitations include but are not limited to: 1.) the client must understand the test results which can be confusing, so I suggest reviewing it with a clinician/health care provider/ physician, etc., 2.) some clients may become fearful of test results, such as a 20% for breast cancer may scare someone for the rest of their life, and 3.) although these tests are great, the environment, as we learned before, can always play a role and alter these results, as it had altered genes in times of famine as seen in the Ghost in Your Genes video.
I believe future applications of Genetic Association studies will be beneficial, however still far from perfect.
First of all, this section in particular reminds me of the movie "GATACA" which, I think, is partially relevant. Although GINA protects us from discrimination based on our genomes, it does not provide restrictions on genetic engineering. I wonder if we will talk more about the ethics and boundaries of genetic engineering in the future.
ReplyDeletePersonally, I've found it very interesting to learn parameters and guidelines for genetic association, especially in the article "How to Use an Article About Genetic Association: C: What Are the Results and Will They Help Me in Caring for My Patients" although the technical aspects were a bit confusing, and I'm wondering if they will be important in class, or whether we will be focusing on a more general understanding. It also seems like the article makes a point to highlight how shaky our understanding is of the relationship between many genes and diseases, which makes me wonder why companies are able to give out reports that are basically educated guesses.
After looking through both articles, I think that genetic association testing is heading in the right direction but there is still a long way to go. Providers and patients need to understand exactly what a genetic test means and how to comprehend the risk factors for a disease better than they do presently. A lot of risk has to do with family history as well and some people may make drastic healthcare decisions if they do not fully understand the testing.
ReplyDeleteAlso, researchers are working on finding genetic associations with other complex diseases such as ADHD, autism, bipolar disorder, depression and schizophrenia, all of which are controversial. If genetic testing comes out about one of these diseases, the researchers are going to have to be positive that the testing is accurate due to the public perception of these diseases. I just think that genetic association testing may lead to "designer babies" or similar types of things where people try to change genetics before a disease can be present, and this is risky in society and would potentially divide society even more, like in the movie "Gattaca" that Audrey mentioned.
Even given the risks and limitations, genetic testing is looking promising for the future. I think that if it does start to find accurate genetic markers for certain diseases though, that the industry will need to be highly regulated by the government or through more laws to keep the testing from getting out of hand. However, I am excited to see what happens in the future with genetic associations.
After reading the various articles about genome wide association studies, the strengths are obvious but it’s important to realize the limitations and be careful while conducting these studies. Overall, GAS provide prognostic information to patients and clinicians; they identify convincing and replicable disease loci for common diseases and provide useful trait mapping. They also identify genetic contributors to common, complex diseases. It is a great strategy when biological pathways are unknown.
ReplyDeleteDespite these strengths come limitations that both patients and clinicians need to be aware of. First off, as others have said, general knowledge about genomics and genetics needs to increase as these tests become more popular. Eliminating any misconceptions and misinterpretations is crucial to the success of these studies. In addition, issues with privacy and discrimination need to be made very clear for each of these studies. Although there is a good foundation for these studies, they still cannot prove causation and are limited to hypothesizing an association. In order to claim there is an association, multiple tests are needed to manage the large amounts of data. This can create a computation and statistical burden, both taking time and money.
However, the future of GAS looks promising as many people are working to minimize these limitations and make the studies stronger. Researchers and physicians are also working to explore to territory by using these studies. For example, in the Neale and Purcell article, they explain how Psychiatric GWAS Consortium, or PGC, is currently working on a comprehensive meta-analysis with focus on ADHD, bipolar disorder, major depression, and schizophrenia. There are choosing to use GWAS for the largest genetic study in psychiatry ever conducted. There are also constantly newly developed technologies which allow more sequencing information to be gained and also reduces costs.
It is amazing how far we’ve come from the beginning of the Human Genome Project to Genetic association. Genetic association allows physicians to see which diseases the patient are more susceptible to in order to take early preventions. For example with Genetic Association, we can determine that one person has high susceptibility for a heart disease, then the physician can recommend certain treatments such as exercise, eating healthy, or other methods that can help prevent heart disease from occurring. Of course with this new field of discovery, there are many things that are still questionable. Currently it is difficult for physicians to explain to their patients about how this works since it is still a new field and even physicians are still uncertain about why some genes behave a certain way. No patients would give consent to attend a clinical trial if they are not aware of the study, so it is important that we can understand Genetic Association enough in order to explain easily, making it available for people to learn about it. Another point which I thought was the most interesting was whether or not it is really better telling the patient they have certain chance of getting certain diseases. After knowing you have a chance or are more susceptible to getting a certain disease, you will be living your life with that in mind forever. I can safely say that some people will be scared and some other people will drastically change their life style, whether for good or bad. Hopefully with time and advancement in technology we will be able to understand Genomics better as a whole.
ReplyDeleteI think genetic testing is a great way to begin personalizing treatment plans tailored to individuals needs and it can also let us know what diseases we are possibly at risk for. This can allow those who may be at risk for certain diseases to take preventative measures to reduce that risk of exacerbating that disease or even prevent it from getting it in the first place. However, even with this great advancement, I definitely agree with Danielle M., that it is still too early for genetic testing to become a major pathway for us to rely on to find out about what disease we may be at risk for. The sound of genetic testing may sound amazing and even unimaginable, which is why some people may rely on it even more, however, I believe the limitations are still too high. At first, I was really excited about the idea of finding out what disease you may have before you are even affected by it, however, the last class changed my mind when we went over the four different testings. Again, like Danielle M. says, the results for all the different testings should be the same. Below average and above average are on the opposite sides of the spectrum, and we shouldn't be giving out that sort of information to patients if the testings aren't accurate. Overall, it may all sound like a good idea, but there should be more research into this so that we can get accurate results. Yes, nothing is accurate but that 1% or 2% can make a huge difference.
ReplyDeleteI think Genetic Association studies have a great amount of potential for providing prognostic information to patients and clinicians. However, additional research is needed in order to make these studies more applicable to the healthcare field. As of right now, there does not seem to be enough information to make conclusive results about how much risk a patient has for a certain disease. Applying these uncertain results may lead to anxiety and stress in the patients. I believe it is more important to focus on behavioral risk factors, such as cigarette smoking and alcohol consumption, because we know that these risk factors play a significant role in the development of disease. Genetic association studies are significant but there is not enough information to apply to the clinical field currently.
ReplyDeleteI believe this ties in with what we talked about in class about DTC genetic tests. These tests are marketed but the results generally have no proven validity or usefulness. These tests were introduced to the public and both the clinicians and patients were not prepared to interpret and understand these results. I believe that before genetic tests can be useful and applicable, the public needs to be educated on how to interpret the results and understand how significant the risk of disease is. Additional research is needed.
I am also a little confused about the Hardy-Weinberg Equilibrium. I understand how to to do the calculations and use the equation but would like to know what the application of these numbers are. Thank you.
Excellent responses, Anya! You completely understand HWE and its application. Professor Chan
DeleteGenetic testing can be a great resource or a great source of anxiety. It is personal and not completely accurate yet. Diseases you may not get can show up in a genetic test causing people to live in fear or a state of limbo. These are reasons why the integration of genetic testing into a mainstreamed hospital environment must be handled with caution and care. Genetic testing has its clear benefits and risks but some of this may not be evident to patients. Getting a genetic test should not be done on an impulse such as DTC tests offer. Genetic counselors need to be widely and inexpensively available to the public so people can be educated about why to test or not and the results of the test. Doctors need to be able to explain to their patients, a basic understanding of genetics. We need to make the tests more accurate and also discover what connection specific genes have to cause onset of disease. This aspect can greatly improve public health. GWAS is one of these crucially important ways to target public health issues in a proactive way. If we can identify selective traits that cause the onset of disease this can become a watershed tool for public health preventing disease in populations. If healthcare workers collaborate to explain benefits and risks of genetic testing we can create an environment where tests can be preventative and change patients lifestyles for the better.
ReplyDeleteAfter reading the articles, it's very clear that GWAS is the future of medicine. Being able to predict future possibilities of disease and even one day customize treatments to fit your own specific genetic profile is exciting to me. That being said, we as consumers must tread lightly. There are so many unknowns in this field. Until more is learned about exactly how our individual SNPs interact with each other to produce genome-based diseases and disorders, we should not be taking the results completely to heart. On top of that, we as consumers must be more responsible with the tests themselves. If you think you may be interested in having your genome profiled, you should talk to you doctor beforehand, so that you may be provided with the correct resources that may aid you in the decision making process. In addition, those of us that do choose to have our genomes profiled should truly have the results interpreted by a professional trained in that field. Having primary care providers interpret genome profiles puts more strain on a group of people that already have their hands full. Overall, the future is promising, but we as consumers must proceed with caution!
ReplyDeleteThe strengths of genetic association is that the data for genes is available. It makes it possible that we figure out what a patient is diagnosed with something beforehand they get into critical condition. It is possible to inform a patient about what risk they have with other illnesses but it it would need more testing in that field. The weaknesses for these testings is that it is hard to maintain all this data. With all the possible gene types, phenotypes that are possible to be obtained and the number of patients going through these test it multiplies the number of genes need to be recorded exponentially. The software available right now to them is unable to keep this all intact. If we moved into a different software like R , Stata, and SAS it would offer many statistical tests and models but be limited in the gene analysis side. For future applications we would need to be able to control data and gene analysis without releasing too much information to the public.
ReplyDeleteI completely agree with you when you say that genetic testing is still in its early years. There’s no doubt in my mind that Genome Wide Association Studies are going to revolutionize our public health system. That being said, I think it’s important to recognize that the Human Genome Project has been completed since February 2001 (That’s 13 years ago!) While we’ve made a tremendous amount of progress in the biotech industry since the conception of the Human Genome Project, we certainly still have a very long way to go. Years back, people were CONVINCED that the Human Genome Project was going to humanity’s greatest achievement and that it’s completion would herald a new age of medical treatments. However, as we’ve learned, this is not the case. The HGP, while a monumental success, has been nothing more than a stepping stone towards refining the field of medicine.
ReplyDeleteMedia hype and researchers in desperate need of grants have repeatedly convinced the public that we’re on the verge of curing any disease because of the recent developments in technology in the past two decades. Of course, science is not as easy as treating a person with drug X when they have genes ABC and they will be 100% fine. I completely support projects like GWAS and the HGP because I know that if we want to continue to advance our understanding of our biology, they’re necessary. However, I think the hype needs to be toned down a bit from scientists and the media alike. In my personal opinion, the public just simply isn’t ready or educated well enough in the field to understand exactly what’s going on in these studies. Hell, scientists barely understand exactly what’s going in these studies; which is exactly why there is so much discrepancy between what certain SNPs mean.
The successful completion of GWAS will certainly be a step in the right direction to refining medicine and aid with prognosis and awareness of diseases. Even so, the is so much ground we need to make before we can begin to conclude anything. Perhaps it’s even possible that GWAS will just become another stepping stone and three decades or so in the future we will need to have massive scale projects involving epigenetic inheritance to obtain an even greater understanding of individuals’ predisposition to disease. But there is no end-all be-all in science and I think that’s something that’s largely forgotten when we study the forefront of science and technology of our age. At best, we can only say that projects like GWAS will help us better understand our biology but anything beyond that can only be speculation.
Patient-Specific Stem Cells Recapitulate Age-Related Macular Degeneration
ReplyDeletehttp://blogs.plos.org/dnascience/2014/02/13/patient-specific-stem-cells-recapitulate-age-related-macular-degeneration/
This study is an interesting example of the current GWA research being conducted. Looking at age-related macular degeneration (AMD), researchers used induced pluripotent stem cells (iPS) to show the relationship between the genetic and environmental risk factors for the disease. In total, age, smoking, and three different genes comprise the major risk factors for AMD. In the case of AMD, the three genes combine to form what is called either a "risk" genotype or a "protective" genotype. Knowing this, the researchers then used the stem cells to see how the two genotypes differ. Skin fibroblasts were taken from 4 patients: 2 without AMD, 1 with 2 copies of the risk genotype, and 1 with 1 risk genotype and 1 protective genotype. The researchers then created the iPS cells from these skin fibroblasts. They then were able to manipulate the cells in different ways to learn more about AMD.
What I found most interesting about this article was the author conceding that, while he once was skeptical about GWAS, this study and the other most recent GWA research were changing his viewpoint. His cited that in the past his concerns over GWAS stemmed from the number of GWAS that were later found to be inaccurate one more research was conducted in the field. However, now that much more genomic research has been conducted, researchers have been able to find precise and accurate results. Specifically, the author states that the number of genome regions looked at and the number of study subjects has increased significantly. It is reasonable to think that the original research in this field faced validity issues simply because it was all so new. However, now that the field has established its bearings and the capacity of the studies has increased, I think we can expect some amazing findings in the next several years.
I found these articles fascinating in that they really seem to be giving a glimpse into the future of medicine. Genome wide association studies are using single genes, or more specifically single nucleotide polymorphism so or SNPs to try and understand common diseases. For me, the idea of using GWAS in order to look at psychiatric disorders is amazing. The area of psychiatric disorders seems to be one that is rarely given attention to, and really stigmatized in society today. Being able to discover the genetic component behind these disorders could be extremely beneficial to those who are predisposed to them.
ReplyDeleteOne of the limitations of these studies is that there are multiple genetic factors that can lead to disease. Disease can be inherited in many different ways, through different SNPs . As the Prader Willi/ Angelman syndromes showed us, the same change in the genome can lead to two completely different diseases. Mapping SNPs in order to track disease may prove to be difficult in that so many different combinations can lead to either the same or different diseases.
Because these studies are focused on finding genetic risk factors, one of the questions one of the articles raised was is this information appropriate for my patient to know. Understanding your risk for a disease can be a good thing, but knowing that you are genetically predisposed to a serious and untreatable disease seems to be a cruel fate. If the GWAS don't lead to new breakthroughs in treatment, then should people allow their genomes to be tested?
I think GWAS are a great start to a new era in understanding disease, and I hope that they will lead to a new era in treating disease as well.
After reading the articles and learning more about Genome-Wide Association, it made me wonder about the actual association between genetic variants/SNPs and disease or illness. While there may be an association between certain SNPs and illness, association doesn't always equal causation.
ReplyDeleteAs I was searching around for general definitions of GWAS I found this link: https://www.genome.gov/20019523#gwas-3
While it is fairly simple and short in its scope, it reminded me of what was meant by association. It says, "However, the associated variants themselves may not directly cause the disease. They may just be "tagging along" with the actual causal variants. For this reason, researchers often need to take additional steps, such as sequencing DNA base pairs in that particular region of the genome, to identify the exact genetic change involved in the disease."
Researchers and those who complete genome sequencing must be aware of when association doesn't directly mean causation. If I were a "consumer" of such genome sequencing and analysis, I would not want to find out later on that a genetic variant I had did not directly relate to the cause of disease.
Despite these concerns, there have been successes with GWAS, as mentioned in the article and by additional articles found in the comments, such as with age-related macular degeneration and "variation in the gene for complement factor H". It is studies like these that present great opportunities and findings to come from genome-wide association studies.
I am very excited by the new discoveries to be made using GWAS in the future. A strength of GWAS is that specific diseases and disorders in the future will be identified through genome association. Meaning a patient can have their genome scanned and told precisely what they could develop later in life. This will increase the accuracy of medical diagnosis. A limitation is that causality generally remains unexplained by GWAS - does having this sequence of genes mean a patient will actually develop a certain disease?
ReplyDeleteI am also particularly interested in how GWAS are being conducted for psychological disorders. The cause of psych disorders are largely unknown due to the fact that we really don't know all that much about the brain. GWAS, however, has made it possible to find out so much more about these disorders through genome association.
After learning about GWAS, I am still curious about how epigenetics fit into this.
According to Attia et al’s article, “initial positive results (for genetic associations) sometimes tend to overestimate the magnitude of the genetic effect… the effect of any single gene is likely to be small… there are potential problems (in) a fundamental assumption, the independence of each genetic effect, may not hold” (305). The article also mentions that there are other clinical predictive variables, such as family history and environmental exposures, which may increase risks for particular diseases. A question that popped in my mind when reading the article was, how valid are genetic associations? Could they be a more reliable predicative factor when it comes to predicting a risk for a particular disease rather than clinical variables? What about for adopted individuals where family history is not known?
ReplyDeleteI think it is important to consider both the nature (gene) and nurture (environment) as predicative variables, and that DTC genetic testing will play an important role in the health field.
Like everyone else, I believe GWAS has great potential to be a huge asset to medicine. It will allow for the individualization of the idea of a healthy lifestyle and will ultimately leave us better informed about diseases we are at risk for. However, although GWAS has the potential to be great and to greatly affect healthcare, I don't believe that it is a tool appropriate for public consumption yet. I believe that GWAS isn't sufficiently developed yet, that results given by DTC private companies are too varied and inconsistent and that we know too little about the trade offs between nature and nurture. Despite what physicians and companies write on their disclaimers, a portion of the public is still likely to misunderstand and underestimate the extent of influence of environmental factors on disease. Just as badly, they may be given incorrect risk estimates and may take such results to heart. As a result, people may become lazy and let their healthy lifestyles slip. They may underestimate the effects of the environment or simply be given an wrong estimation of risk. I want to believe in GWAS and the awareness and understanding that it could bring to people about what lies in their own genes, but I don't think it's being held to the standard that it needs to be at right now. And for it to be subpar but available to the public, to me, is dangerous.
ReplyDeleteIn a sense, genetic wide association studies (GWAS) are very similar to case-control studies. Case-control studies enroll participants with a disease of interest and then compare them to a control group of people who do not have the disease. Ultimately, through this methodology case-control studies look for risk factors that might be associated with the occurrence of the disease. GWAS are similar in that they compare SNP variations in genomes from people with a disease of interest to SNP variations in genomes from people without a disease of interest (control). If the genomes with the disease of interest have a higher frequency of a SNP compared to the group of genomes without the disease, then it is assumed that there is an association between the SNP variation and the disease.
ReplyDeleteThe comparability between GWAS and case-control studies means that they have similar strengths and weaknesses. GWAS strengths are that they are a fast way to look for risk associations. Instead of having to look at multiple genomes over an extended period of time for the occurrence of a SNP variation leading to a disease, we can look at genomes with a disease and compare them to genomes without a disease. Thereby we can find associations between SNP variations and disease occurrence.
However, the weakness with GWAS is that because they aren't looking at genetic changes over time, they never provide conclusive evidence as to what gene mutations cause a disease. We can only find associations. In other words, results from GWAS should always be taken with a grain of salt and should be analyzed critically before using the results in a clinical setting.
Another limitation that arises from GWAS studies is that finding control groups can be especially difficult. Even though we are all 99.99% the same, the small amount of genetic variation we have is significant when trying to create a control group for a GWAS. The question arises: How do we make sure that when we conduct a GWAS we are using an appropriate control group as a comparison?
While there are weaknesses to GWAS, I think they have a great potential to be of benefit to society as a whole. Being able to use the findings from these studies to advise people how to reduce their risk for certain diseases is powerful, and can ultimately change the landscape of health care to one that is more preventive rather than reactionary.
I think genetic association studies show a lot of promise for the future. From the articles, it seems like there are many cases in which diseases are “strongly heritable,” and finding which genes are associated with the disease would be very helpful for future treatment or at least early detection. However, there can be arguments against GWAS (genome wide association studies) if there is low clinical utility for the study. If people find out that they are genetically predisposed for a disease, but there are no precautions that they can take, it will cause stress. A positive would be if someone found out they were genetically predisposed for a disease, but there were preventative measures they could take against the disease, and there were lifestyle factors that they could change to be proactive. It is important for GWAS to consider family history of a particular disease. There are still many limitations with GWAS that need to be overcome, but with the positives that we can already see, I think GWAS will potentially be very helpful in finding causes of diseases in the future.
ReplyDeleteGenome-Wide association studies seem to me to be the best way to target gene(s) that cause disease. Though there are some limitations to GWAS, such as the fact that multiple genes can cause the same disease and that environmental factors often contribute heavily to disease, I think GWAS is a useful tool for finding out what genes can greatly increase your risk of a certain disease. If we are able to find the genes that cause a disease, we can then create drugs to help cure or at least manage the disease for those who are suffering.
ReplyDeleteI think GWAS will lead to more people being aware of their genes and if they're predisposed to certain disease, and will really open up the field of genetic counselors. Genetic counselors will really be key once GWAS is more common and people can find out if they have genes that cause a certain disease because they will need to be taught what having that gene really means and how they can lessen their chances of getting the disease or how to deal with the reality of having a genetic disorder, such as Huntington's.
Both of the articles mentioned the endless innovative possibilities that Genetic Association studies can yield. In class this week, I also learned that Genome Wide Association Studies (GWAS) examine the small effects of multiple genes in common "complex" diseases such as diabetes or cancer. Whereas Single Gene Disorder Studies look at large effects of a single gene in diseases such as sickle cell anemia.
ReplyDeleteGWAS identify associations between specific outcomes and genetic variants across the entire genome, rather than in a specific gene. This method identifies markers or small variants that are common in the general population and may or may not have known functional consequences. One of the advantages that comes with Genetic Association studies is that it can be used to test a specific marker in a particular gene, like individual SNPs for example. These studies can also be useful in investigating gene-gene or gene-environment interactions. As we've learned before, the environment certainly has a big influence on modifying our genes; therefore, it is important to consider these external factors. Another advantage is that the biological pathway of the trait does not have to be known in order for that trait to be examined.
Although genetic association studies can provide promising results, they still have certain limitations. These studies cannot test causality since they can only measure statistical associations. The only way to know causality is to understand the biological pathway and the role that the gene variant has in the production of the trait or disease process. GWAS are also prone to confounding variables. Moreover, these studies can be expensive, especially if they are prospective cohort studies.
In order to genetic association studies to be more practical in the future, they need to have larger sample sizes so that they can detect an association in cases where multiple genes are involved in a disease.
In the future, after improvements are made in the cost and efficiency of genome-wide association studies, health professionals will be able to use such tools to provide patients with individualized information about their risks of developing certain diseases. The information will enable health professionals to tailor prevention programs to each person's unique genetic makeup. In addition, if a patient does become ill, the information can be used to select the treatments most likely to be effective and least likely to cause adverse reactions in that particular patient.
I didn't know much about GWAS before this class, so I find everything related to GWAS very interesting. What I find most interesting is how they are going about finding which genes cause which diseases. While it seems that GWAS is still in the relatively early stages, this could be a huge breakthrough for the future of medicine. I think it's extremely important that we're able to trace diseases back to the genes they're associated with. This way, we could be able to prevent or even eradicate certain diseases if we were able to use gene therapy methods to combat the diseases. With early enough gene intervention, we could stop the disease from ever manifesting. However, I think a lot more needs to be done to improve and perfect GWAS before it's accepted by everyone and widely used. This could be a great education tool for patients to know their potential risks for diseases.
ReplyDeleteBefore reading these two articles, I had a very limited understanding of the complexity of Genome Wide Association studies. I knew that studies of the sort would require large sample sizes, could potentially be time consuming and of course costly, however I was not expecting just how complex they were. I think that this is an excellent up and coming form of genetic study that can be integrated into the clinical setting, once it becomes more easily and accessible. With the help of SNP chips and online resources such as GAIN and WTCCC, time commitments have been cut, as well as costs. I was very surprised by something mentioned in the article "The Positives, Protocols, and Perils of Genome-Wide Association." This article describes the types of diseases that have been tested using GWA, and among those are tuberculosis, coronary heart disease, type 1 and type 1 diabetes, rheumatoid arthritis, Crohn's disease, bipolar disorder and hypertension. I was not expecting there to be issues with GWA studies and bipolar disorder. These studies have shown to be not as helpful in the study of psychiatric disorders such as bipolar disorder, as they are in the study of metabolic studies. I had always thought that to a certain degree, psychiatric disorders could be studied through genetics, and it seems that this is more difficult than I had initially thought. Genome-Wide Association studies can become very beneficial tool for diagnostic purposes in the clinical setting once things become more easily accessible, functional and cost/time effective. I am also very curious to see what the future holds for the role of GWA and psychiatric disorder studies.
ReplyDeleteI believe that genetic association studies can be very helpful in a clinical setting, if it is appropriate. What struck me most about this article was that patients who knew and disclosed their genetic knowledge could be discriminated against, especially with life insurance or health insurance access. That is something I had not though of before. I believe that genetic association should continue to be improved, and should only be used for serious illnesses, if possible. The article's discussion about anxiety and stress resulting from the patient's knowledge of their genes also resonated with me. It is very true that a lifetime of anxiety and stress over the possibility of developing a disease will have detrimental health effects, and I am not sure that a telling a patient of their possible disease development would be the most beneficial course of action. Below is a study I found where researchers performed a genetic association test for a "smoking gene." This is an example of something that could help patients, but also harm them. They could avoid tobacco if they find that they have a gene for it, but health insurance companies and employers could also deny them coverage for that gene, since it is a risk.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202555/
I agree with many of the other classmates in the idea that GWAS are very useful to determining the etiology of these diseases and also can provide more information to be used in further research of these particular diseases.
ReplyDeleteI also agree with Rebecca from above in the fact that I thought it was interesting in the article "How to Use an Article About Genetic Association C: What Are the Results and Will They Help Me in Caring for My Patients?" by Attia et al. that certain diseases can be more common across certain ethnic groups compared to other ethnic groups or they can be more similar in the prevalence across ethnic groups. While doing some research online, I stumbled across this article about a study that was done in Europe. This GWAS looked at the genomes of thousands of people from four different continents, 20 countries, and consisted of four different ethnic groups. This GWAS study looked at the genome in relation to Type 2 diabetes. They discovered two regions, close to the genes ARL15 and RREB1, that related to higher levels of insulin and glucose, which are risk factors for Type 2 diabetes. This study found that there were more similarities in the genetic variation across ethnic groups for Type 2 diabetes than there were differences. That is really interesting to me because usually you hear about one ethnic group being more prone to diabetes than the other. However, this study found different results. As mentioned in the article, the GWAS studies are a good way to open up a new perspective and new results to provide a new pathway of research for obtaining further information for not only diabetes, but other diseases as well. Therefore, I think GWAS are really helpful. The more information that can be found on genetics and disease, the better our understanding will be.
http://www.redorbit.com/news/health/1113067432/diabetes-genetics-study-brings-in-different-ethnic-group-data-021014/
The Human Genome Project and the HapMap Project were completed in 2003 and 2005, respectively, and in the past decade, their completions have allowed researchers many success in conducting GWAS. Researchers have identified genetic variations as risk factors for various common diseases such as type 2 diabetes, mental illnesses, heart disease, cancer, and obesity. Each of these diseases is very complex and surely caused by a multitude of factors; therefore, I think the fact that we can associate polymorphisms with diseases brings us closer to fully understanding the causes of disease and how best to treat disease. There are, of course, limitations to GWAS. The associations found by GWAS are by no means causations. Of two individuals with the same variation in a gene, one could have the disease associated with the variation while the other could be disease-free. The variations determined by GWAS are merely risk factors for diseases. Additionally, I think it is important to note that it can be difficult to replicate the results of a GWAS, which can lead to false positives. However, despite these limitations, I think the future of GWAS looks extremely bright. If applied effectively, GWAS will mark the era of personalized treatment and prevention.
ReplyDeleteGenome Wide Association Studies are an amazing step forward in the medical field of research. I knew GWAS is improving research in areas like breast or other cancers, but I had no idea it could extend to areas such as obesity or Parkinson's disease. It is truly amazing how many different disorders that are so prevalent now can be associated with a combination of different genes and SNPs. It is obvious that GWAS have many strengths in improving understanding in complex, often chronic diseases or disorders. I had no idea genes had such a far reaching effect on so many different disorders that so often seem to be due to environment and behaviors, like obesity. I think finding treatments or better prevention methods from GWAS is a huge possibility for these disorders that have been so prevalent recently but we have not yet been able to find successful treatment or prevention for. These disorders have been increasing steadily due to recent social trends, (aging population or increasingly high priced healthy foods among other things), and the fact that GWAS could help to complete our understanding of these disorders and hopefully impede their progress is so important to helping society. I never realized how far genetics and genomics could go in helping understand and hopefully treat such important disorders.
ReplyDeleteThrough the assigned readings and our class discussions, I've learned a great deal about Genetic Wide Association Studies that I hadn't known before. It was made very clear through all that we've discussed around GWAS that it has the potential to yield beneficial and promising outcomes. One thing that stood out to me most was how GWAS are able to examine the very small effects of multiple genes in common complex diseases that a single gene disorder study do not have the ability to identify. I also found it really interesting how GWAS can be used to trace back the etiology of diseases and how this information can be used to work towards generating prevention methods for common complex diseases like diabetes and cancer. I think if implemented in the proper setting, GWAS can go very far to help generate prevention methods and treatments for a variety of disorders.
ReplyDeleteOver the last few lectures we have learned more about Direct-to-Consumer genetic testing and its advantages and disadvantages. A few issues have arisen since the inception of DTC companies and the wide availability of genetic information offered to consumers. In class we looked at the results of the Government Accounting Office (GAO) Report that was conducted in 2006 to determine the reliability between the results between DTC companies that offered genetic information. The results of this study showed that DTC genetic tests between companies varied, which could result in misleading information to the consumer. This really got me thinking about the major advantages and disadvantages for the consumer. Should these tests still be offered as a way to allow people to know their risks of developing certain diseases, or should we keep genetic matters strictly through the physician? I agree with the notion that genetic counselors should become more widely available for patients in the doctors office if patients do want to be aware of their risk of developing disease. These counselors can help correctly interpret the genetic test results to consumers in order to avoid the possibility of misinterpretation of risks.
ReplyDeleteIn the article that Sawyer mentioned in "The Atlantic," Uzbekistan is using genetic testing to place athlete in a certain sport to have the best team for the olympics.
ReplyDeleteI am appalled by this idea. I believe that genetic testing should be for use of benefiting a patient or to prevent or predict diseases. It is crazy in my eyes to see others using genetic testing to place athletes. Soon enough people will be wanting to use our genes to figure what we should study in college and what profession everyone should have.
This process is of course in development and I agree with the american commentaries saying that Uzbekistan is trying to make a decision based on a few genes when they dont know the role of the other genes. Their decision to use genetics to see what sport someone should play is not going to be accurate enough. One commentary said that they are better off using a stop watch then checking someones genetic makeup. I found this to be comical and this idea to be a waste of time for athletes in Uzbekistan.
This idea of using genes for placement of some sort reminds me of a movie 'Gattaca' (1997). About a man who wants to be an astronaut but only can do so if he has perfect genes. In the world of Gattaca, there is no such thing as a resume, jobs only check your genetic makeup to accept you in a field. I highly recommend this movie.
The articles from this week opened my eyes to a world that I thought only existed in nonfiction. Though these ideas may have great potential. It could have some negative effects for future generations. Being too knowledgable about one's own genes could be equally as harming as not knowing anything at all. This is especially true when we learn about the affect of the environment on ourselves.
After learning about the applications of Genome-Wide Association Studies, it is evident that these studies have significant potential and yield beneficial information for patients. With any new technology or advances in science there are limitations, however, with time these limitations could be reduced. GWAS has many strengths, such as the ability to determine expected risks for particular diseases in individuals and providing prognostic information to clinicians. This type of information could allow patients to avoid harmful actions or implement beneficial behavior. Additionally, GWAS provides genetic information across generations, making it possible for scientists to study genetically inherited diseases and determine possible causes. Unfortunately, there are some weaknesses and limitations to these studies. Positive results can lead to overestimation of the genetic effects and lead to biased estimated of treatment results. Small studies may also fail to determine an association since they lack power. GWAS also requires many assumptions to be made, such as the assumption that each genetic effect is independent of other factors, which is not always the case. It is also required that these studies adjust for other factors such as age, gender, family history, etc. These tests may also promote adverse consequences such as unnecessary anxiety and fear. General knowledge about genetics in the medical field tends to be poor, especially in the primary care field and often there is a lack of oversight of genetic testing. Patient's privacy and discrimination also becomes a concern when using GWAS.
ReplyDeleteI was surprised by how many assumptions must be made when utilizing HWE. It seems as though the results would be extremely inaccurate since all the assumptions are assuming unrealistic factors. In reality, natural selection, mutation, migration, random mating and chance events are very prevalent in today's society.
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ReplyDeleteI think the Genome Wide association studies will revolutionize medicine and public health in the next 30-50 years. Once we know the genetic cause or risk or the disease, we will be able to better prevent it, and maybe even cure it. I also think it is amazing that they are researching genetic associations with obesity. Usually I just think of obesity as having to do with diet, and behavior, but it makes sense that there would be genes linked with it. This is very important considering obesity is one of the biggest public health problems of the 21st century. It will be interesting to see if they could use gene therapy to replace those genes.
ReplyDeleteGenome-wide association studies has made big breakthroughs in the last decade that help us further clarify and reveal the mystery behind genes. Admittedly, coming into class, I really had no idea, nor the understanding, of what GWAS is or does. However, I realize now that this study is important to unlocking more doors that the human genome is still hiding from scientists and researchers. The study of these many individual genes show that each one has an impact on our lives, no matter how big or small it be. Genes such as a mutated BRCA1/2 affecting the risk chance for breast cancer or a mutated HLA-DR3/4 that increases the chance to develop diabetes are just two of many genes that have been studied intensively because of the high rate the disease occurs in a population. However, there are still so many genes that have to be researched to see what kind of link it holds to certain interactions within our body. GWAS has the potential to reveal these said links, but because the study is still very young, it may take several decades before a full description of what each gene does is released.
ReplyDeleteIn the meantime, I believe scientists and researchers should reach out to the public and discuss more about DTC. By educating the masses, people will come to realize how important DTC on genetic information will be, and how these genes may be manipulated for the benefit of a person.
Great article.
ReplyDeleteThis makes your point about GWAS providing advances in modern healthcare. Our class is mostly focused on the public health aspect of genomics and in identifying genes that can cause disorders and disease we can be able to develop treatments. The article you picked out has already identified several promising treatments for Alzheimer's. However, there are pros and cons to GWAS, it is important to consider whether the benefits outweigh the cost. After all that we have discussed in class, I am persuaded that mostly good can and will come from GWAS. Targeting genes that have negative outcomes and applying therapy either in vitro or during a lifetime are all options that we have. It's great.
It seems my computer really dislikes either me or blogspot... But here is the post I wrote:
ReplyDeleteGenome wide association studies have great potential as another clinical tool in measuring our risk for certain diseases and how we can alter our lifestyle choices to decrease our chances for developing said diseases.
But like every research method, GWAS does have its limitations. For example, patients who receive a minor chance developing a disease may assume that in order to be perfectly healthy, they should have a 0% chance of developing the disease. Along with such technological advancements, clinicians need to further educate and consult with their patients about such results and what they mean. This way, the patients can make informed decisions about their lifestyle, instead of assuming that a low-risk for disease means an automatic death sentence.
GWAS is a great tool for research and should be further developed, but as with most technological advancements, the public needs to fully understand the results from it before altering their lifestyles and making decisions.
I learned a lot about GWAS. Prior to this class I did not know anything about Genome Wide Association Studies. I think GWAS is a great public health approach to understanding and treating diseases. GWAS allows treatment to be more specific because we can learn about the various genes associated with a disease. GWAS will provide more efficient treatment options.
ReplyDeleteCurrently, US spends the most on healthcare however, our quality of care is not up to par with the other developed nations. GWAS will help improve quality of care in the US because we can develop drugs that target genes that are causing a specific disease. I believe that more research needs to be done to understand disease pattern on a genetic level.