Sex-Specific Genetic and Transcriptomic Liability to Neuroticism.
Biomarkers
GWAS
Neuroticism
Pituitary gland
Sex effects
TWAS
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
01 02 2023
01 02 2023
Historique:
received:
02
03
2022
revised:
08
06
2022
accepted:
13
07
2022
pubmed:
17
10
2022
medline:
28
12
2022
entrez:
16
10
2022
Statut:
ppublish
Résumé
The presentation, etiology, and relative risk of psychiatric disorders are strongly influenced by biological sex. Neuroticism is a transdiagnostic feature of psychiatric disorders displaying prominent sex differences. We performed genome-wide association studies of neuroticism separately in males and females to identify sex-specific genetic and transcriptomic profiles. Neuroticism scores were derived from the Eysenck Personality Inventory Neuroticism scale. Genome-wide association studies were performed in 145,669 females and 129,229 males from the UK Biobank considering autosomal and X chromosomal variation. Two-sided z tests were used to test for sex-specific effects of discovered loci, genetic correlates (n = 673 traits), tissue and gene transcriptomic profiles, and polygenic associations across health outcomes in the Vanderbilt University Biobank (39,692 females and 31,268 males). The single nucleotide polymorphism heritability of neuroticism was not statistically different between males (h Through a comprehensive assessment of genetic risk for neuroticism and the associated biological processes, this study identified several molecular pathways that can partially explain the known sex differences in neurotic symptoms and their psychiatric comorbidities.
Sections du résumé
BACKGROUND
The presentation, etiology, and relative risk of psychiatric disorders are strongly influenced by biological sex. Neuroticism is a transdiagnostic feature of psychiatric disorders displaying prominent sex differences. We performed genome-wide association studies of neuroticism separately in males and females to identify sex-specific genetic and transcriptomic profiles.
METHODS
Neuroticism scores were derived from the Eysenck Personality Inventory Neuroticism scale. Genome-wide association studies were performed in 145,669 females and 129,229 males from the UK Biobank considering autosomal and X chromosomal variation. Two-sided z tests were used to test for sex-specific effects of discovered loci, genetic correlates (n = 673 traits), tissue and gene transcriptomic profiles, and polygenic associations across health outcomes in the Vanderbilt University Biobank (39,692 females and 31,268 males).
RESULTS
The single nucleotide polymorphism heritability of neuroticism was not statistically different between males (h
CONCLUSIONS
Through a comprehensive assessment of genetic risk for neuroticism and the associated biological processes, this study identified several molecular pathways that can partially explain the known sex differences in neurotic symptoms and their psychiatric comorbidities.
Identifiants
pubmed: 36244801
pii: S0006-3223(22)01448-2
doi: 10.1016/j.biopsych.2022.07.019
pmc: PMC10508260
mid: NIHMS1927364
pii:
doi:
Substances chimiques
ASXL3 protein, human
0
HSP27 Heat-Shock Proteins
0
HSPB2 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
243-252Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NIDCD NIH HHS
ID : R21 DC018098
Pays : United States
Organisme : NIMH NIH HHS
ID : F32 MH122058
Pays : United States
Organisme : NIDA NIH HHS
ID : R33 DA047527
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Informations de copyright
Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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