GWAS on psychological traits like major depressive disorder (h2SNP = 0.06)1, intelligence (h2SNP = 0.20)2 and neuroticism (h2SNP range: 0.09–0.15)3,4 have uncovered numerous associated variants. These genome-wide significant single-nucleotide polymorphisms (SNPs), however, explain only a small portion of the twin heritability (h2twin = 0.40, 0.54, and 0.47, respectively)5. The small individual SNP effects support the infinitesimal model, which assumes the involvement of many genetic variants (i.e., polygenicity), each of (very) small effect, such that large sample sizes are required to robustly detect them.
