GWAS: heritability missing in action?
The missing heritability discussion continues in this letter. They do acknowledge gene-gene interactions and cite a few of my papers.
Clarke AJ, Cooper DN. GWAS: heritability missing in action? Eur J Hum Genet. 2010 [PubMed]
"So, where is this ‘missing heritability’? We respond to this question in two different ways. First, we believe that complex disorders are indeed complex and that genetic studies of complex disorders in humans face a number of challenges including gene–gene and gene–environment interactions and epigenetic modification of the genome. Second, we shall argue that high estimates of heritability have been misinterpreted as showing that a predisposition to such a condition (one with high heritability) must have been transmitted through the family from parent to child. The complexity of these common conditions is apparent from the range of factors that need to be considered as potentially contributing to the ‘missing heritability’. These can be rare variants whose significance is not yet recognised, less uncommon variants of small effect, or common variants of very small effect (very weakly penetrant)."