Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits.

Female Genome-Wide Association Study Humans Male Multifactorial Inheritance Phenotype Polymorphism, Single Nucleotide Sex Characteristics
Behavioral GWAS Genetic correlation Heritability Psychiatric Sex differences

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
15 06 2021
Historique:
received: 14 05 2020
revised: 15 12 2020
accepted: 17 12 2020
pubmed: 3 3 2021
medline: 29 6 2021
entrez: 2 3 2021
Statut: ppublish

Résumé

The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits. Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (r We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior). Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.

Sections du résumé

BACKGROUND
The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a sex-differentiated genetic architecture within and between traits.
METHODS
Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (r
RESULTS
We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior).
CONCLUSIONS
Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.

Identifiants

DOI: 10.1016/j.biopsych.2020.12.024 PMID: 33648717 PMC: PMC8163257
pubmed: 33648717
pii: S0006-3223(21)00033-0
doi: 10.1016/j.biopsych.2020.12.024
pmc: PMC8163257
pii:
doi:

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

1127-1137

Subventions

Organisme : NCI NIH HHS
ID : R01 CA229618
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102371
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105746
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101519
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103537
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109539
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH119243
Pays : United States
Organisme : NIMH NIH HHS
ID : K01 MH113848
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114924
Pays : United States

Investigateurs

Martin Alda (M)
Marco Bortolato (M)
Christie L Burton (CL)
Enda Byrne (E)
Caitlin E Carey (CE)
Lauren Erdman (L)
Laura M Huckins (LM)
Manuel Mattheisen (M)
Elise Robinson (E)
Eli Stahl (E)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Références

CNS Drugs. 2006;20(2):107-23
pubmed: 16478287
Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):439-447
pubmed: 30708398
Science. 2018 Jun 22;360(6395):
pubmed: 29930110
Nat Genet. 2019 Mar;51(3):431-444
pubmed: 30804558
Cell. 2019 Dec 12;179(7):1469-1482.e11
pubmed: 31835028
JAMA Psychiatry. 2020 Feb 1;77(2):155-164
pubmed: 31746968
Nat Genet. 2015 Jul;47(7):702-9
pubmed: 25985137
Science. 2019 Jul 19;365(6450):
pubmed: 31320509
Nat Rev Genet. 2019 Oct;20(10):567-581
pubmed: 31171865
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14372-14377
pubmed: 27911795
Nat Commun. 2019 Feb 8;10(1):666
pubmed: 30737381
Nat Genet. 2017 Nov;49(11):1584-1592
pubmed: 28604731
Hum Brain Mapp. 2016 Nov;37(11):3733-3744
pubmed: 27246897
Genetics. 2017 Feb;205(2):979-992
pubmed: 27974502
Genome Biol. 2016 Jul 29;17(1):166
pubmed: 27473438
J Child Psychol Psychiatry. 2003 Nov;44(8):1092-115
pubmed: 14626453
Nat Neurosci. 2018 Dec;21(12):1656-1669
pubmed: 30482948
Mol Psychiatry. 2017 Oct;22(10):1376-1384
pubmed: 28937693
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
JAMA Psychiatry. 2014 May;71(5):573-81
pubmed: 24806211
PLoS Genet. 2015 Oct 01;11(10):e1005378
pubmed: 26426971
Nat Genet. 2021 May;53(5):663-671
pubmed: 33888908
Biol Psychiatry. 2018 Jun 15;83(12):1044-1053
pubmed: 29325848
Dialogues Clin Neurosci. 2016 Dec;18(4):425-436
pubmed: 28179814
Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):428-438
pubmed: 30593698
Nat Rev Genet. 2019 Mar;20(3):173-190
pubmed: 30581192
Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):351-364
pubmed: 30456828
PLoS Genet. 2016 Nov 15;12(11):e1006425
pubmed: 27846226
Nat Genet. 2019 Sep;51(9):1339-1348
pubmed: 31427789
Nat Genet. 2019 Feb;51(2):277-284
pubmed: 30510236
PLoS One. 2017 Jul 27;12(7):e0181038
pubmed: 28749953
Nat Genet. 2016 Dec;48(12):1462-1472
pubmed: 27798627
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
JAMA Psychiatry. 2019 Mar 1;76(3):259-270
pubmed: 30649197
Genet Epidemiol. 2020 Apr;44(3):283-289
pubmed: 31961015
Am J Epidemiol. 2017 Nov 1;186(9):1026-1034
pubmed: 28641372
Nature. 2016 May 11;533(7604):539-42
pubmed: 27225129
Neuropsychopharmacology. 2019 Jan;44(1):59-70
pubmed: 30030541
Clin Pharmacol Ther. 2008 Sep;84(3):362-9
pubmed: 18500243
Nat Genet. 2021 Sep;53(9):1283-1289
pubmed: 34493869
Transl Psychiatry. 2018 Sep 4;8(1):178
pubmed: 30181555
J Abnorm Psychol. 2012 Feb;121(1):282-8
pubmed: 21842958
Mol Psychiatry. 2018 Mar;23(3):666-673
pubmed: 28439101
Biol Psychiatry. 2022 Jan 1;91(1):102-117
pubmed: 34099189

Auteurs

Joanna Martin (J)

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom. Electronic address: martinjm1@cardiff.ac.uk.

Ekaterina A Khramtsova (EA)

Section of Genetic Medicine, Department of Medicine and Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois; Computational Sciences, Janssen Pharmaceuticals, Spring House, Pennsylvania.

Slavina B Goleva (SB)

Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee.

Gabriëlla A M Blokland (GAM)

Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands.

Michela Traglia (M)

Department of Psychiatry, University of California San Francisco, San Francisco, California; Institute for Human Genetics, University of California San Francisco, San Francisco, California; Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California.

Raymond K Walters (RK)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

Christopher Hübel (C)

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Jonathan R I Coleman (JRI)

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, United Kingdom.

Gerome Breen (G)

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Maudsley Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, United Kingdom.

Anders D Børglum (AD)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Ditte Demontis (D)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Jakob Grove (J)

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Department of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark.

Thomas Werge (T)

Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health, University of Copenhagen, Copenhagen, Denmark; Section for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Copenhagen, Denmark.

Janita Bralten (J)

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Cynthia M Bulik (CM)

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Phil H Lee (PH)

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Carol A Mathews (CA)

Department of Psychiatry, University of Florida, Gainesville, Florida; Genetics Institute, University of Florida, Gainesville, Florida.

Roseann E Peterson (RE)

Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.

Stacey J Winham (SJ)

Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.

Naomi Wray (N)

Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.

Howard J Edenberg (HJ)

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.

Wei Guo (W)

Genetic Epidemiology Research Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.

Yin Yao (Y)

School of Life Sciences, Fudan University, Shanghai, China.

Benjamin M Neale (BM)

Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Stephen V Faraone (SV)

Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, New York; Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, New York.

Tracey L Petryshen (TL)

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Lauren A Weiss (LA)

Department of Psychiatry, University of California San Francisco, San Francisco, California; Institute for Human Genetics, University of California San Francisco, San Francisco, California; Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California.

Laramie E Duncan (LE)

Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.

Jill M Goldstein (JM)

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Jordan W Smoller (JW)

Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Barbara E Stranger (BE)

Section of Genetic Medicine, Department of Medicine and Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois; Center for Genetic Medicine, Department of Pharmacology, Northwestern University, Chicago, Illinois.

Lea K Davis (LK)

Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: lea.k.davis@gmail.com.

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Classifications MeSH

questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Examining Sex-Differentiated Genetic Effects...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Examining Sex-Differentiated Genetic Effects...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Hérédité multifactorielle › Examining Sex-Differentiated Genetic Effects...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Examining Sex-Differentiated Genetic Effects...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Examining Sex-Differentiated Genetic Effects...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Caractères sexuels › Examining Sex-Differentiated Genetic Effects...