Renowned geneticist Jay Shendure wrote an editorial titled ‘life after genetics’ (h/t: gholson lyon), but based on the content, it should have been titled ‘life after GWAS’. It is good news that Shendure is discussing after-life, which means the GWAS era is over.
The article is very similar to various commentaries in our blog, but presented in polite language. For example, instead of describing various large GWAS studies as abysmal failures, Shendure called them ‘successes’, yet asked for ‘shift its attention from disease gene identification to following through on next steps, most importantly pursuing the biological mechanisms underlying genotype-phenotype associations’.
The most noteworthy section of Shendure’s editorial is the following:
Fourth, although genomics provides a systematic, genome-wide means of identifying a gene or genes in which variation contributes to the pathophysiology of a given disease, understanding the role of these gene(s) inevitably requires experiments. This is ostensibly a task for biologists rather than geneticists; however, geneticists bear some degree of responsibility for ensuring that the story does not end with genetics and, as such, there should be no barriers against geneticists delving deeply into the biology of gene mechanisms. Furthermore, the number of genes implicated by genetic approaches in human phenotypes but whose biological function remains poorly understood is easily in the thousands. The armamentarium of genomic approaches for observational (for example, transcriptional profiling) and perturbational (for example, genome-wide knockdown or knockout screens) experiments may represent useful approaches for advancing our fundamental understanding of the biological role(s) of implicated genes in a scalable fashion.
Interpretation: “Enough of that ‘let us statisticians keep finding potential disease genes, while you biologists suffer in the lab’ crap. Go to the lab yourself and show that your predictions are anything worth paying attention to.”
Needless to say that the answer of the other side will be to redefine the word phenotype and continue wasting money in worthless large-scale studies (check - ‘Tragedy of the Day New Revealing Human Transcriptome Paper at Biorxiv’).