Dissatisfaction in social relationships is reported widely across many psychiatric conditions. We investigated the genetic architecture of family relationship satisfaction and friendship satisfaction in the UK Biobank. We leveraged the high genetic correlation between the two phenotypes (rg = 0.87 se = 0.03; P < 2.2x10-16) to conduct multi-trait analysis of Genome Wide Association Study (GWAS) (Neffective family = 164,112; Neffective friendship = 158,116). We identified two genome-wide significant associations for both the phenotypes: rs1483617 on chromosome 3 and rs2189373 on chromosome 6, a region previously implicated in schizophrenia. eQTL and chromosome conformation capture in neural tissues prioritizes several genes including NLGN1. Gene-based association studies identified several significant genes, with highest expression in brain tissues. Genetic correlation analysis identified significant negative correlations for multiple psychiatric conditions including highly significant negative correlation with cross-psychiatric disorder GWAS, underscoring the central role of social relationship dissatisfaction in psychiatric diagnosis. The two phenotypes were enriched for genes that are loss of function intolerant. Both phenotypes had modest, significant additive SNP heritability of approximately 6%. Our results underscore the central role of social relationship satisfaction in mental health and identify genes and tissues associated with it.

Genome-wide association study of social relationship satisfaction: significant loci and correlations with psychiatric conditions