Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders.
Bipolar Disorder
/ genetics
Depressive Disorder, Major
/ genetics
Endothelial Cells
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Polymorphism, Single Nucleotide
Psychotic Disorders
/ genetics
Receptors, Vascular Endothelial Growth Factor
Schizophrenia
/ genetics
Sex Characteristics
Sulfurtransferases
Bipolar disorder
Genome-wide association study
Genotype-by-sex interaction
Major depressive disorder
Schizophrenia
Sex differences
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
01 01 2022
01 01 2022
Historique:
received:
06
08
2020
revised:
11
02
2021
accepted:
12
02
2021
pubmed:
9
6
2021
medline:
5
1
2022
entrez:
8
6
2021
Statut:
ppublish
Résumé
Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10 In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Sections du résumé
BACKGROUND
Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk.
METHODS
We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH.
RESULTS
Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10
CONCLUSIONS
In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Identifiants
pubmed: 34099189
pii: S0006-3223(21)01139-2
doi: 10.1016/j.biopsych.2021.02.972
pmc: PMC8458480
mid: NIHMS1685139
pii:
doi:
Substances chimiques
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
MOCOS protein, human
EC 2.8.1.-
Sulfurtransferases
EC 2.8.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102-117Subventions
Organisme : NIMH NIH HHS
ID : R01 MH104964
Pays : United States
Organisme : NIMH NIH HHS
ID : U54 MH118919
Pays : United States
Organisme : Medical Research Council
ID : G0901310
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH123451
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH092380
Pays : United States
Investigateurs
Stephan Ripke
(S)
Benjamin M Neale
(BM)
Aiden Corvin
(A)
James T R Walters
(JTR)
Kai-How Farh
(KH)
Peter A Holmans
(PA)
Phil Lee
(P)
Brendan Bulik-Sullivan
(B)
David A Collier
(DA)
Hailiang Huang
(H)
Tune H Pers
(TH)
Ingrid Agartz
(I)
Esben Agerbo
(E)
Margot Albus
(M)
Madeline Alexander
(M)
Farooq Amin
(F)
Silviu A Bacanu
(SA)
Martin Begemann
(M)
Richard A Belliveau
(RA)
Judit Bene
(J)
Sarah E Bergen
(SE)
Elizabeth Bevilacqua
(E)
Tim B Bigdeli
(TB)
Donald W Black
(DW)
Richard Bruggeman
(R)
Nancy G Buccola
(NG)
Randy L Buckner
(RL)
William Byerley
(W)
Wiepke Cahn
(W)
Guiqing Cai
(G)
Dominique Campion
(D)
Rita M Cantor
(RM)
Vaughan J Carr
(VJ)
Noa Carrera
(N)
Stanley V Catts
(SV)
Kimberly D Chambert
(KD)
Raymond C K Chan
(RCK)
Ronald Y L Chen
(RYL)
Eric Y H Chen
(EYH)
Wei Cheng
(W)
Eric F C Cheung
(EFC)
Siow Ann Chong
(SA)
C Robert Cloninger
(CR)
David Cohen
(D)
Nadine Cohen
(N)
Paul Cormican
(P)
Nick Craddock
(N)
James J Crowley
(JJ)
David Curtis
(D)
Michael Davidson
(M)
Kenneth L Davis
(KL)
Franziska Degenhardt
(F)
Jurgen Del Favero
(J)
Ditte Demontis
(D)
Dimitris Dikeos
(D)
Timothy Dinan
(T)
Srdjan Djurovic
(S)
Gary Donohoe
(G)
Elodie Drapeau
(E)
Jubao Duan
(J)
Frank Dudbridge
(F)
Naser Durmishi
(N)
Peter Eichhammer
(P)
Johan Eriksson
(J)
Valentina Escott-Price
(V)
Laurent Essioux
(L)
Ayman H Fanous
(AH)
Martilias S Farrell
(MS)
Josef Frank
(J)
Lude Franke
(L)
Robert Freedman
(R)
Nelson B Freimer
(NB)
Marion Friedl
(M)
Joseph I Friedman
(JI)
Menachem Fromer
(M)
Giulio Genovese
(G)
Lyudmila Georgieva
(L)
Ina Giegling
(I)
Paola Giusti-Rodríguez
(P)
Stephanie Godard
(S)
Jacqueline I Goldstein
(JI)
Vera Golimbet
(V)
Srihari Gopal
(S)
Jacob Gratten
(J)
Lieuwe de Haan
(L)
Christian Hammer
(C)
Marian L Hamshere
(ML)
Mark Hansen
(M)
Thomas Hansen
(T)
Vahram Haroutunian
(V)
Annette M Hartmann
(AM)
Frans A Henskens
(FA)
Stefan Herms
(S)
Joel N Hirschhorn
(JN)
Per Hoffmann
(P)
Andrea Hofman
(A)
Mads V Hollegaard
(MV)
David M Hougaard
(DM)
Masashi Ikeda
(M)
Inge Joa
(I)
Antonio Julià
(A)
René S Kahn
(RS)
Luba Kalaydjieva
(L)
Sena Karachanak-Yankova
(S)
Juha Karjalainen
(J)
David Kavanagh
(D)
Matthew C Keller
(MC)
James L Kennedy
(JL)
Andrey Khrunin
(A)
Yunjung Kim
(Y)
Janis Klovins
(J)
James A Knowles
(JA)
Bettina Konte
(B)
Vaidutis Kucinskas
(V)
Zita Ausrele Kucinskiene
(ZA)
Hana Kuzelova-Ptackova
(H)
Anna K Kähler
(AK)
Claudine Laurent
(C)
Jimmy Lee Chee Keong
(J)
S Hong Lee
(SH)
Sophie E Legge
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Bernard Lerer
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Miaoxin Li
(M)
Tao Li
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(CM)
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(EA)
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(C)
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(LM)
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(APS)
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(L)
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(A)
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(P)
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(M)
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Yin Yao
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Kristjar Skajaa
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Michael Owen
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Robert H Yolken
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Niels Plath
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Jonathan Mill
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Daniel Geschwind
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Informations de copyright
Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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