ArticleBiological psychiatry2021
Examining Sex-Differentiated Genetic Effects Across Neuropsychiatric and Behavioral Traits.
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Article in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 3 of them syntheses that pooled it.
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58citing papers in PubMed, 3 pooled it
14.2field-weighted citation impact, top 1% of its field
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Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 85 citations in OpenAlex.
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- Sex-Specific Association Between Genetic Risk of Psychiatric Disorders and Cardiovascular Diseases.Circulation. Genomic and precision medicine · 2024Article
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Authors and funding
33 authors at 20 institutions in 7 countries.
Joanna MartinMRC 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 KhramtsovaSection 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 GolevaDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee.
Gabriëlla A M BloklandPsychiatric & 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 TragliaDepartment 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 WaltersAnalytic 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 HübelSocial, 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 ColemanSocial, 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 BreenSocial, 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 BørglumThe 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 DemontisThe 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 GroveThe 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 WergeInstitute 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 BraltenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Cynthia M BulikDepartment 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 LeeDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Carol A MathewsDepartment of Psychiatry, University of Florida, Gainesville, Florida; Genetics Institute, University of Florida, Gainesville, Florida.
Roseann E PetersonDepartment of Psychiatry, Virginia Commonwealth University, Richmond, Virginia; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
Stacey J WinhamDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
Naomi WrayInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Howard J EdenbergDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
Wei GuoGenetic Epidemiology Research Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Yin YaoSchool of Life Sciences, Fudan University, Shanghai, China.
Benjamin M NealeAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Stephen V FaraoneDepartment 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 PetryshenDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Lauren A WeissDepartment 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 DuncanDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Jill M GoldsteinDepartment 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 SmollerPsychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Barbara E StrangerSection 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 DavisDivision 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.
Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium
Harvard University · USAarhus University · DKUniversity of California, San Francisco · USCardiff University · GBNational Health Service · GBVanderbilt University Medical Center · USBroad Institute · USFudan University · CNIndiana University School of MedicineKing's College London · GBMayo Clinic in Florida · USNational Institutes of Health · USNorthwestern University · USRadboud University Nijmegen · NLStanford University · USSUNY Upstate Medical University · USThe University of Queensland · AUUniversity of Chicago · USUniversity of Copenhagen · DKUniversity of Florida · US
Funding
Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3MGenetic Privacy and Identity in Community Settings - GetPreCiSeRM1HG009034 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CLAYTON, ELLEN WRIGHT, MALIN, BRADLEY A. · 2016 to 2024
$8.3MIntegrating Common and Rare Variation to Discover Genes Associated with Tourette SyndromeR01NS102371 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MATHEWS, CAROL A, OPHOFF, ROEL A · 2018 to 2022
$7.4M2/7 Psychiatric Genomics Consortium: Finding Actionable VariationU01MH109539 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI DALY, MARK JOSEPH · 2016 to 2020
$4.7MAnalysis, Validation and Resource Creation for Genome Sequencing of Complex DiseasesU01HG009086 · NHGRI · VANDERBILT UNIVERSITY · PI COX, NANCY J, LI, BINGSHAN · 2016 to 2020
$4.3MCross-Population Working Group on Genes and Environment in Major Depression (POP-GEM): Advancing the Understating of Etiology through DiversityR01MH125938 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI Roseann Elizabeth Peterson · 2022 to 2026
$4.2MDiscovering Biology for Neuropsychiatric Diseases Through Omics Studies on ComorbiditiesR01MH113362 · NIMH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COX, NANCY J, KNAPIK, ELA W · 2017 to 2021
$3.9MLongitudinal Family/Molecular Genetic Study to Validate Research Domain CriteriaR01MH101519 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI FARAONE, STEPHEN V, GLATT, STEPHEN J · 2014 to 2018
$3.5MLarge-Scale Collaborative Genetic and Epigenetic Studies of Tourette SyndromeR01NS105746 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MATHEWS, CAROL A, PASCHOU, PERISTERA · 2019 to 2023
$3.1M7/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109532 · NIMH · WASHINGTON UNIVERSITY · PI AGRAWAL, ARPANA, EDENBERG, HOWARD J · 2016 to 2020
$3.1MGenetic mechanisms underlying sexual dimorphism in cancer and response to therapyR01CA229618 · NCI · UNIVERSITY OF COLORADO DENVER · PI HUANG, RONG STEPHANIE, STRANGER, BARBARA E · 2019 to 2024
$2.9M5/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109514 · NIMH · CARDIFF UNIVERSITY · PI O'DONOVAN, MICHAEL · 2016 to 2020
$2.9MNCI NIH HHS R01 CA229618NHGRI NIH HHS RM1 HG009034NHGRI NIH HHS U01 HG009086NICHD NIH HHS P50 HD103537NIMH NIH HHS K01 MH113848NIMH NIH HHS R00 MH101367NIMH NIH HHS R01 MH101519NIMH NIH HHS R01 MH113362NIMH NIH HHS R01 MH114924NIMH NIH HHS R01 MH119243NIMH NIH HHS R01 MH125938NIMH NIH HHS U01 MH109499NIMH NIH HHS U01 MH109501NIMH NIH HHS U01 MH109514NIMH NIH HHS U01 MH109528NIMH NIH HHS U01 MH109532NIMH NIH HHS U01 MH109536NIMH NIH HHS U01 MH109539NINDS NIH HHS R01 NS102371NINDS NIH HHS R01 NS105746Wellcome Trust
Abstract
backgroundThe 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.
methodsUsing 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
resultsWe 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).
conclusionsSex 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.
Indexed as
Genome-Wide Association StudyMultifactorial InheritanceFemaleHumansMalePhenotypePolymorphism, Single NucleotideSex CharacteristicsBehavioralGenetic correlationGWASHeritabilityPsychiatricSex differences
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