Sex differences in the genetic architecture of obsessive-compulsive disorder.
Adult
Case-Control Studies
Databases, Genetic
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
/ methods
Genomics
/ methods
Humans
Male
Obsessive-Compulsive Disorder
/ genetics
Phenotype
Polymorphism, Single Nucleotide
/ genetics
Receptors, Glutamate
/ genetics
Sex Factors
genetics
genome-wide association study
obsessive compulsive disorder
sex differences
sex-specific analysis
sex-specific genetic architecture
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN: 1552-485X
Titre abrégé: Am J Med Genet B Neuropsychiatr Genet
Pays: United States
ID NLM: 101235742
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
06
02
2018
revised:
24
09
2018
accepted:
25
09
2018
pubmed:
21
11
2018
medline:
16
7
2020
entrez:
21
11
2018
Statut:
ppublish
Résumé
Obsessive-compulsive disorder (OCD) is a highly heritable complex phenotype that demonstrates sex differences in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sex differences including a sex-dependent liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, and sex-specific pleiotropic effects. Furthermore, we tested the hypothesis that genetic heterogeneity between the sexes may obscure associations in a sex-combined genome-wide association study. We observed a strong genetic correlation between male and female OCD and no evidence for a sex-dependent liability threshold model, suggesting that sex-combined analysis does not suffer from widespread loss of power because of genetic heterogeneity between the sexes. While we did not detect any significant sex-specific genome-wide single nucleotide polymorphisms (SNP) associations, we did identify two significant gene-based associations in females: GRID2 and GRP135, which showed no association in males. We observed that the SNPs with sexually differentiated effects showed an enrichment of regulatory variants influencing expression of genes in brain and immune tissues. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific genetic risk factors for OCD.
Identifiants
pubmed: 30456828
doi: 10.1002/ajmg.b.32687
pmc: PMC6527502
mid: NIHMS993656
doi:
Substances chimiques
Receptors, Glutamate
0
glutamate receptor delta 2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-364Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000430
Pays : United States
Organisme : David Judah Foundation
ID : S40024
Pays : International
Organisme : NIMH NIH HHS
ID : R01 MH079487
Pays : United States
Organisme : NIMH NIH HHS
ID : K23 MH085057
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH071507
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH094267
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH079488
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109539
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA MH002930-06
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109528
Pays : United States
Organisme : NIMH NIH HHS
ID : R13 MH073250
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS040024
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH087748
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH079494
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS040024
Pays : United States
Organisme : Biological Sciences Division at the University of Chicago
Pays : International
Informations de copyright
© 2018 Wiley Periodicals, Inc.
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