The observed difference in estimates of variance explained based on a sample of ‘unrelateds' (that is, not affected by common environmental influences and/or pedigree structure) and of variance explained based on a sample of ‘relateds' (that is, possibly affected by common environmental influences and/or pedigree structure), especially for neuroticism, informs on the poor outcomes reported to date from GWAS of major depressive disorder.67 Future research may consider possible environmental factors that dilute associations between genetic polymorphisms and the trait in the classic GWAS design.
