"Tens of Thousands of Associations but No Causal Mechanisms Revealed: Mismatches between GWAS and Developmental Molecular Biology"

Lowe and Reddy conclude: “As of February 2015, genome-wide association studies (GWAS) and other studies had demonstrated the association of more than 15,000 SNPs with a complex disease or trait (Welter et al. 2014). However,... [ view full abstract ]

Lowe and Reddy conclude: “As of February 2015, genome-wide association studies (GWAS) and other studies had demonstrated the association of more than 15,000 SNPs with a complex disease or trait (Welter et al. 2014). However, the mechanisms underlying these associations remain largely undefined. More generally, the underlying architecture of complex diseases and traits remains poorly defined.” Here I consider whether we should be surprised at the disparity between apparent successes of GWAS (and other related techniques) and lack of success at isolating underlying genetic mechanisms for the relevant traits. I argue that we should not be surprised and proceed by examining the mismatch in methods and assumptions between GWAS and related techniques on the one hand and developmental molecular biology on the other. I argue that Richard Lewontin’s (1974) conclusions about mismatches between high heritability measures and claims about genetic causation can be applied here. I support my claim that Lewontin’s arguments are relevant to this issue by looking at a few detailed examples of contrasting genetic approaches to human traits.