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 common factor that contributes to psychiatric and psychotic traits. Our results show that SIB contributes a small heritable component, which is associated genetically with other social traits such as friendship as well as psychiatric disorders.

社会孤立与一系列精神问题有关，但导致社会孤立的行为因素尚不清楚。在这里，进行了一项全基因组关联研究 (GWAS)，以识别英国生物银行多达 449,609 名参与者中专门导致社会孤立行为 (SIB) 的遗传变异。鉴定出 17 个具有全基因组意义的位点，有助于基于 SNP 的遗传力估计 4%。使用 SIB GWAS，在 ASPAC（一个独立的发育队列）中得出多基因风险评分 (PRS)，并用于测试与自我报告的友谊分数的关联，包括与 12 岁和 18 岁的友谊质量和数量相关的项目确定遗传倾向是否在儿童发育过程中表现出来。 18 岁时，友谊分数与 SIB PRS 相关，这表明遗传因素可以预测青春期后期的相关社会特征。使用 SIB GWAS 的连锁不平衡 (LD) 评分相关性证明了与自闭症谱系障碍 (ASD)、精神分裂症、重度抑郁症 (MDD)、教育程度、外向性和孤独感的遗传相关性。然而，使用保守的孟德尔随机化方法，没有发现 SIB 与任一方向的任何特征之间存在因果关系的证据。基因组结构方程模型 (SEM) 揭示了导致 SIB、神经质、孤独、MDD 和 ASD 的一个共同因素，与导致精神病和精神病特征的第二个共同因素微弱相关。我们的研究结果表明，SIB 贡献了一个小的遗传成分，它与其他社会特征（如友谊和精神疾病）在遗传上相关。