Polygenic risk of social isolation behavior and its influence on psychopathology and personality

作者：Adam Socrates, Niamh Mullins, Ruben C. Gur, Raquel E. Gur, Eli A. Stahl, Paul F. O’Reilly, Abraham Reichenberg, Hannah Jones, Stanley Zammit, Eva Velthorst · 发表于：Molecular Psychiatry · 年份：2024 · DOI：10.1038/s41380-024-02617-2 · 被引用次数：15 · 研究领域：Genetic Associations and Epidemiology、Autism Spectrum Disorder Research、Health disparities and outcomes

Social isolation has been linked to a range of psychiatric issues, but the behavioral component that drives it is not well understood. Here, a genome-wide associations study (GWAS) was carried out to identify genetic variants that contribute specifically to social isolation behavior (SIB) in up to 449,609 participants from the UK Biobank. 17 loci were identified at genome-wide significance, contributing to a 4% SNP-based heritability estimate. Using the SIB GWAS, polygenic risk scores (PRS) were derived in ALSPAC, an independent, developmental cohort, and used to test for association with self-reported friendship scores, comprising items related to friendship quality and quantity, at age 12 and 18 to determine whether genetic predisposition manifests during childhood development. At age 18, friendship scores were associated with the SIB PRS, demonstrating that the genetic factors can predict related social traits in late adolescence. Linkage disequilibrium (LD) score correlation using the SIB GWAS demonstrated genetic correlations with autism spectrum disorder (ASD), schizophrenia, major depressive disorder (MDD), educational attainment, extraversion, and loneliness. However, no evidence of causality was found using a conservative Mendelian randomization approach between SIB and any of the traits in either direction. Genomic Structural Equation Modeling (SEM) revealed a common factor contributing to SIB, neuroticism, loneliness, MDD, and ASD, weakly correlated with a second c...