genome-wide association studies
dgmacarthur | July 19, 2010Every issue of Nature Genetics is packed full of them, and they're the basis for the risk predictions offered by every personal genomics company - but how do you make sense of a genome-wide association study? How can you tell the difference between results you can trust and those you should treat with caution?
Over at Genomes Unzipped, Jeff Barrett (who's authored more GWAS than most) explains some of the key features of these studies, and what to keep an eye out for when interpreting their results.
dgmacarthur | July 7, 2010As an addendum to my previous post on the controversial "longevity genes" study, you should go and check this out. It's a post on the blog of personal genomics company 23andMe, and it's a pretty impressive piece of scientific dissection of the longevity GWAS paper - in addition to detailing a variety of methodological problems with the study, the authors actually used the 23andMe database to look at the predictive value of the longevity GWAS algorithm on their own customers:
We took a preliminary look in our customer data to see if the proposed SNP-based model described in Sebastiani et al.…
dgmacarthur | July 7, 2010When an article was published in Science last week reporting that DNA samples from exceptionally long-lived individuals differed detectably from those of normal individuals, it got plenty of positive attention from the mainstream media. However, the buzz from experts was rapid and telling: my colleagues in the statistical genetics community weren't excited about the results, but immediately, profoundly skeptical.
For people who've spent years doing genome-wide association studies (GWAS), several things stand out as unusual from this paper: the very large effect sizes of the identified SNPs (…
dgmacarthur | April 29, 2010Kai Wang is a postdoctoral fellow at the Center for Applied Genomics, Children's Hospital of Philadelphia and an author on numerous genome-wide association studies. He left this lengthy comment as a response to my recent post on this comment by McClellan and King in Cell, and I felt it warranted promotion to a full post (with Kai's permission). For more discussion of the M&K review see also two recent posts by Steve Turner at Getting Genetics Done, and an excellent post from p-ter at Gene Expression.
A similar version of this comment is also published at Getting Genetics Done. I've done…
dgmacarthur | April 26, 2010This critique of genome-wide association studies by Jon McClellan and Mary-Claire King in Cell is the latest salvo in a prolonged backlash against genome-wide association studies (GWAS).
I hope to have more on the McClellan and King paper shortly, but in the meantime I will point you to a positive take on the paper by Stephen Turner (read the comments section), and an excellent response to one of M&K's more bizarre criticisms by p-ter at Gene Expression. The claim in question is that the tendency of GWAS to find disease associations outside of protein-coding genes is somehow a problem;…
dgmacarthur | March 31, 2010
Wellcome Trust Case Control Consortium. (2010). Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls Nature, 464 (7289), 713-720 DOI: 10.1038/nature08979
The Wellcome Trust Case Control Consortium has just published the results of a massive survey of common, large DNA duplications and deletions (collectively termed copy number variation, or CNVs) in 16,000 patients suffering from complex diseases and 3,000 controls. The results come as no surprise, but are nonetheless disappointing: the study identified absolutely no novel CNVs…
dgmacarthur | March 11, 2010Nic Wade says something very strange in his most recent article on whole genome sequencing in reference to the outcomes of genome-wide association studies:
The results of this costly international exercise have been disappointing. About 2,000 sites on the human genome have been statistically linked with various diseases, but in many cases the sites are not inside working genes, suggesting there may be some conceptual flaw in the statistics.
Erm... or maybe many common variants affecting the risk of complex diseases simply aren't found in protein-coding regions? That's the (biologically…
dgmacarthur | November 11, 2009Medland et al. (2009). Common Variants in the Trichohyalin Gene Are Associated with Straight Hair in Europeans. The American Journal of Human Genetics DOI: 10.1016/j.ajhg.2009.10.009
A couple of weeks ago I reported on a presentation by 23andMe's Nick Eriksson at the American Society of Human Genetics meeting in Honolulu, in which Eriksson presented data on a series of genome-wide association studies performed by the company using genetic and trait data from its customers.
Along with genetic analysis of a variety of other traits (such as asparagus anosmia and photic sneeze) Eriksson…
dgmacarthur | October 25, 2009It's been an intensive week of genomics here at the American Society of Human Genetics meeting, and I haven't been able to grab time to blog as much as I'd have liked. In fact there's a whole load of genomics news I'll be trying to cover in some detail over the next couple of weeks; for the moment, though, I couldn't let today's presentation from personal genomics company 23andMe go by without at least some comment. (For other coverage of the conference, do check out Luke Jostins' blog coverage and the stream of live analysis on Twitter.)
The 23andMe presenter (Nick Eriksson) delivered an…
dgmacarthur | October 13, 2009 Details are pretty sketchy, but a press release announced today suggests that personal genomics company 23andMe has performed a genome-wide association study comparing 100 current or former professional NFL players with a set of controls of unspecified sample size.
The shocking result:
The study did not find the tested players to be genetic outliers, suggesting that genetics may not be a good predictor of athletic success.
It's unsurprising that the results of this study are negative (more on this below), but the conclusions they draw from this are fallacious. In fact we know from twin and…
dgmacarthur | July 17, 2009Purcell et al. (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder Nature DOI: 10.1038/nature08185
Neil Walker has been doing a spectacular job of serving up useful information in the comments recently, so I asked him to write the first ever guest post on Genetic Future - something that (as I will be announcing shortly) I intend to do fairly regularly over the next couple of months.
The topic is a paper that has created a rather perplexed buzz recently in the complex disease genetics community: the genome-wide association study (GWAS) for…
dgmacarthur | May 20, 2009BioArray News (subscription required) reports that genomic analysis technology provider Illumina has launched a new family of genotyping chips designed to simultaneously assay 4 million sites of variation in the human genome.
The chips are a major step up from the 1-million-feature chips that
currently represent the state of the art, and take advantage of several
public projects generating catalogues of human genetic variation (such
as the 1000 Genomes Project).
Illumina has also increased the density of markers in and around genes,
and fleshed out regions that have previously been…
dgmacarthur | April 28, 2009A new paper in Nature reports the results of a large genome-wide association of autism. After some fairly heroic data analysis, the researchers have managed to tag one region of the genome as containing a common variant that contribute to the disease, with odds ratios on the order of 1.2 (the paper actually reports six variants in the same region, but these all appear to be tagging the same underlying causal variant).
The finding is getting fairly glowing press coverage, but let's keep it in context: an odds ratio of 1.2 means that individuals carrying the variant have their risk of the…
dgmacarthur | April 28, 2009Cho, Y., Go, M., Kim, Y., Heo, J., Oh, J., Ban, H., Yoon, D., Lee, M., Kim, D., Park, M., Cha, S., Kim, J., Han, B., Min, H., Ahn, Y., Park, M., Han, H., Jang, H., Cho, E., Lee, J., Cho, N., Shin, C., Park, T., Park, J., Lee, J., Cardon, L., Clarke, G., McCarthy, M., Lee, J., Lee, J., Oh, B., & Kim, H. (2009). A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits Nature Genetics, 41 (5), 527-534 DOI: 10.1038/ng.357
A paper just released in Nature Genetics takes the most comprehensive look yet at the genetic factors…
dgmacarthur | April 21, 2009I wrote a few days ago about a debate in the New England Journal of Medicine over the value of data emerging from recent genome-wide studies of the role of genetic variation in common human diseases and other traits. David Goldstein argued that genome-wide association studies (GWAS) have generated disappointing results, and should be scaled back in favour of whole-genome sequencing; Joel Hirschhorn responded with an upbeat piece emphasising the insights generated by GWAS into the molecular basis of common diseases.
Now geneticist Steve Jones has an opinion piece in the Telegraph that…
dgmacarthur | April 16, 2009The latest issue of the New England Journal of Medicine has four excellent and thought-provoking articles on the recent revolution in the genetics of common disease and its implications for personalised medicine and personal genomics. Razib and Misha Angrist have already commented, and there's also a thorough lay summary by Nick Wade in the NY Times.
The scene is set by a brief but useful review of progress in genome-wide studies of human disease, which is worth reading if you need to get yourself up to speed on the scope of progress in modern disease genomics. The main course, however, is…
dgmacarthur | March 3, 2009Yurii S Aulchenko, Maksim V Struchalin, Nadezhda M Belonogova, Tatiana I Axenovich, Michael N Weedon, Albert Hofman, Andre G Uitterlinden, Manfred Kayser, Ben A Oostra, Cornelia M van Duijn, A Cecile J W Janssens, Pavel M Borodin (2009). Predicting human height by Victorian and genomic methods European Journal of Human Genetics DOI: 10.1038/ejhg.2009.5
Human height is a strongly genetic trait: in well-nourished Westerners somewhere in the vicinity of 80-90% of the variation in height is due to genetic factors; if your parents are tall, there's a very good chance you will be too. That means…
dgmacarthur | February 9, 2009I'll be uploading a few of what I saw as the highlights from the AGBT meeting over the next week or so, as I go over my notes - you can also browse over Anthony Fejes' blog for live-blogging of many of the sessions. In no particular order, here are some of the tid-bits gleaned from Friday's sessions.
Kari Stefansson gave an overview of some of the latest results coming out from deCODE Genetics. He argued that combining multiple genetic variants for common diseases can now give clinically useful results - e.g. their work on thyroid cancer (published today in Nature Genetics) shows that the 3.7…
dgmacarthur | January 19, 2009
Welcome to the 42nd edition of Gene Genie, the blog carnival of clinical genetics and personalised medicine.
Most of the entries in this edition fall under the broad umbrella of personalised genetics, with posts emphasising both the pros and cons of the emerging consumer genetic testing industry.
The promise and perils of personalised genetics
Hsien-Hsien Li from Eye on DNA warned about the potential dangers of pressuring kids to compete in athletic events based on genetic testing results, citing the suicide of a 15-year-old Singaporean boy. Alberto from Medical Pills used Hsien's post as a…
dgmacarthur | January 19, 2009Well, it's a little late, but I finally have a list of what I see as some of the major trends that will play out in the human genomics field in 2009 - both in terms of research outcomes, and shifts in the rapidly-evolving consumer genomics industry.
For genetics-savvy readers a lot of these predictions may seem, well, predictable, so I want to emphasise that my purpose here is not really to make risky forecasts; I'm more interested in laying out what I see as the major big picture trends for the year to come, with a few specific predictions about unknowns thrown in. In any case (as you will…