New Dustup Over Genome-Scanning Studies

A harsh takedown of a popular type of human genetics study in the pages of Cell has prompted a chatter of commentary online, and at least one researcher plans to submit a response to the journal. Psychiatrist Jon McClellan and geneticist Mary-Claire King, both of the University of Washington, Seattle, wrote earlier this month that genome-wide association studies (GWAS), which scan large stretches of the genomes of hundreds of people for common gene variants driving common diseases, aren't getting us very far. "It is now clear that common risk variants fail to explain the vast majority of genetic heritability for any human disease," they wrote in an essay, arguing that many of the hundreds of GWAS findings to date "stem from factors other than a true association with disease risk." In other words, they're not conveying anything about one's likelihood of developing ailments such as diabetes, heart disease, or cancer.

The two listed a number of reasons for this but said that ultimately it comes down to biology. They believe that common variants simply don't have much to do with most diseases studied in GWAS. Instead, McClellan and King think we ought to pay more attention to rare variants that arose in our genomes relatively recently. (King is famous for discovering one such variant, the breast cancer gene BRCA1).

"Although I wholeheartedly agree that rare variants play a substantial role in human diseases, I also think that the section on GWAS reflects misunderstandings of the concept of GWAS, ignorance of standard practices in GWAS, misinterpretation of published primary research data, and as a result, is misinforming the general readership of Cell," wrote Kai Wang, a postdoc at Children's Hospital of Philadelphia whose papers were cited in the Cell article. Like many others, he believes that GWAS have had a major impact on our understanding of the human genome, and he plans to send comments to Cell.

Others in the community are buzzing about the paper here, here, and here.