Chunk #111 — 5. Implications for understanding gene-brain-behavior relationships in health and disease — 5.1. Intermediate phenotypes, or “endophenotypes”
One of the issues that used to be frequently mentioned in relation to GWAS has been so called “missing heritability”, i.e. the fact that genetic variants identified by GWAS can account only for a small portion of heritability. However, more recent GWAS studies were able to capture an increasingly large proportion of the phenotypic variation, especially when all SNPs, rather than only GWAS “hits”, are considered. As GWAS efforts continue and sample sizes grow to tens or even hundreds of thousands, it becomes clear that the perceived failure or disappointment about GWAS was overstated (Visscher et al., 2012). Vissher et al. underscore that the aim of GWAS is to detect loci that are associated with complex traits, rather than explain all genetic variation, and this aim is being successfully achieved by GWAS studies that have led to new discoveries about genes and pathways involved in common diseases and other complex traits (Visscher et al., 2012). However, most of these recent successes concerned “somatic” phenotypes such as auto-immune or metabolic diseases, while the progress in the identification of loci associated with
