Genomic analysis of mental illness: a changing landscape.

摘要

Marked genetic heterogeneity in psychiatric disease challenges the "common disease-common variant" model, which posits that complex disorders stem from the collective effects of common variants, each conferring a small degree of risk. Rare and common disease alleles are not mutually exclusive, and in principle both could play some role. However, results from genome-wide association studies (GWAS) fail to explain the vast majority of genetic heritability for any human disease, either individually or collectively.5 There are now sufficient GWAS for schizophrenia to conclude that there are no common risk variants of even moderate effect (eg, an odds ratio >1.5).