Polygenic risk of social isolation behavior and its influence on psychopathology and personality.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
30 May 2024
30 May 2024
Historique:
received:
22
02
2023
accepted:
16
05
2024
revised:
02
05
2024
medline:
30
5
2024
pubmed:
30
5
2024
entrez:
29
5
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38811692
doi: 10.1038/s41380-024-02617-2
pii: 10.1038/s41380-024-02617-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust (Wellcome)
ID : 217065/Z/19/Z)
Organisme : NIMH NIH HHS
ID : R01 MH128971
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH119219
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : R01MH128971
Informations de copyright
© 2024. Crown.
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