Greater male than female variability in regional brain structure across the lifespan,Human Brain Mapping

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Greater male than female variability in regional brain structure across the lifespan
Human Brain Mapping ( IF 3.5 ) Pub Date : 2020-10-12 , DOI: 10.1002/hbm.25204
Lara M Wierenga _{1,

2} , Gaelle E Doucet _{3,

4} , Danai Dima _{5,

6} , Ingrid Agartz _{7,

8,

9} , Moji Aghajani _{10,

11,

12} , Theophilus N Akudjedu _{13,

14} , Anton Albajes-Eizagirre _{15,

16,

17} , Dag Alnaes _{7,

18} , Kathryn I Alpert ₁₉ , Ole A Andreassen _{7,

18} , Alan Anticevic ₂₀ , Philip Asherson ₂₁ , Tobias Banaschewski ₂₂ , Nuria Bargallo _{23,

24} , Sarah Baumeister ₂₂ , Ramona Baur-Streubel ₂₅ , Alessandro Bertolino ₂₆ , Aurora Bonvino ₂₆ , Dorret I Boomsma ₂₇ , Stefan Borgwardt _{28,

29} , Josiane Bourque _{30,

31} , Anouk den Braber _{27,

32} , Daniel Brandeis _{22,

33,

34,

35} , Alan Breier ₃₆ , Henry Brodaty _{37,

38} , Rachel M Brouwer ₃₉ , Jan K Buitelaar _{40,

41} , Geraldo F Busatto ₄₂ , Vince D Calhoun ₄₃ , Erick J Canales-Rodríguez _{15,

16} , Dara M Cannon ₁₃ , Xavier Caseras ₄₄ , Francisco X Castellanos _{45,

46} , Tiffany M Chaim-Avancini ₄₂ , Christopher Rk Ching ₄₇ , Vincent P Clark _{48,

49} , Patricia J Conrod _{31,

50} , Annette Conzelmann _{51,

52} , Fabrice Crivello ₅₃ , Christopher G Davey _{54,

55} , Erin W Dickie _{56,

57} , Stefan Ehrlich ₅₈ , Dennis Van't Ent ₂₇ , Simon E Fisher _{59,

60} , Jean-Paul Fouche ₆₁ , Barbara Franke _{60,

62,

63} , Paola Fuentes-Claramonte _{15,

16} , Eco Jc de Geus ₂₇ , Annabella Di Giorgio ₆₄ , David C Glahn _{65,

66} , Ian H Gotlib ₆₇ , Hans J Grabe _{68,

69} , Oliver Gruber ₇₀ , Patricia Gruner ₂₀ , Raquel E Gur _{30,

71} , Ruben C Gur ₃₀ , Tiril P Gurholt _{7,

18} , Lieuwe de Haan ₇₂ , Beathe Haatveit _{7,

18} , Ben J Harrison ₇₃ , Catharina A Hartman ₇₄ , Sean N Hatton _{75,

76} , Dirk J Heslenfeld ₇₇ , Odile A van den Heuvel _{10,

78} , Ian B Hickie ₇₅ , Pieter J Hoekstra ₇₉ , Sarah Hohmann ₂₂ , Avram J Holmes _{20,

80,

81} , Martine Hoogman _{60,

62} , Norbert Hosten ₈₂ , Fleur M Howells _{83,

84} , Hilleke E Hulshoff Pol ₃₉ , Chaim Huyser _{85,

86} , Neda Jahanshad ₄₇ , Anthony C James _{87,

88} , Jiyang Jiang ₃₇ , Erik G Jönsson _{7,

9} , John A Joska ₈₄ , Andrew J Kalnin ₈₉ , , Marieke Klein _{39,

60,

62} , Laura Koenders ₇₂ , Knut K Kolskår _{18,

90,

91} , Bernd Krämer ₇₀ , Jonna Kuntsi ₂₁ , Jim Lagopoulos _{92,

93} , Luisa Lazaro _{16,

94,

95,

96} , Irina S Lebedeva ₉₇ , Phil H Lee _{81,

98} , Christine Lochner ₉₉ , Marise Wj Machielsen ₁₀₀ , Sophie Maingault ₁₀₁ , Nicholas G Martin ₁₀₂ , Ignacio Martínez-Zalacaín _{103,

104} , David Mataix-Cols ₉ , Bernard Mazoyer _{105,

106} , Brenna C McDonald ₁₀₇ , Colm McDonald ₁₃ , Andrew M McIntosh ₁₀₈ , Katie L McMahon _{109,

110} , Genevieve McPhilemy ₁₃ , Dennis van der Meer _{7,

18,

111} , José M Menchón _{16,

103,

104} , Jilly Naaijen ₄₀ , Lars Nyberg _{112,

113} , Jaap Oosterlaan _{114,

115} , Yannis Paloyelis ₆ , Paul Pauli _{116,

117} , Giulio Pergola _{26,

118} , Edith Pomarol-Clotet _{15,

16} , Maria J Portella _{16,

119} , Joaquim Radua _{9,

15,

16,

17,

120} , Andreas Reif ₁₂₁ , Geneviève Richard _{7,

18} , Joshua L Roffman ₁₂₂ , Pedro Gp Rosa ₄₂ , Matthew D Sacchet ₁₂₃ , Perminder S Sachdev _{37,

124} , Raymond Salvador _{15,

16} , Salvador Sarró _{15,

16} , Theodore D Satterthwaite ₃₀ , Andrew J Saykin _{107,

125} , Mauricio H Serpa ₄₂ , Kang Sim _{126,

127} , Andrew Simmons ₁₂₈ , Jordan W Smoller _{81,

129} , Iris E Sommer ₁₃₀ , Carles Soriano-Mas _{16,

103,

131} , Dan J Stein ₁₃₂ , Lachlan T Strike ₁₃₃ , Philip R Szeszko _{3,

134} , Henk S Temmingh ₈₄ , Sophia I Thomopoulos ₄₇ , Alexander S Tomyshev ₉₇ , Julian N Trollor ₃₇ , Anne Uhlmann _{84,

135} , Ilya M Veer ₁₃₆ , Dick J Veltman ₁₃₇ , Aristotle Voineskos ₅₆ , Henry Völzke _{138,

139,

140} , Henrik Walter ₁₃₆ , Lei Wang ₁₉ , Yang Wang ₁₄₁ , Bernd Weber ₁₄₂ , Wei Wen ₃₇ , John D West ₁₀₇ , Lars T Westlye _{7,

18,

90} , Heather C Whalley _{108,

143} , Steven Cr Williams ₁₄₄ , Katharina Wittfeld _{68,

69} , Daniel H Wolf ₃₀ , Margaret J Wright _{133,

145} , Yuliya N Yoncheva ₁₄₆ , Marcus V Zanetti _{42,

147} , Georg C Ziegler ₁₄₈ , Greig I de Zubicaray ₁₁₀ , Paul M Thompson ₄₇ , Eveline A Crone _{1,

2,

149} , Sophia Frangou _{3,

150} , Christian K Tamnes _{7,

8,

151}

Affiliation

Institute of Psychology, Leiden University, Leiden, The Netherlands.
Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Boys Town National Research Hospital, Omaha, Nebraska, USA.
Department of Psychology, School of Arts and Social Sciences, City, University of London, London, UK.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
Department of Research & Innovation, GGZ inGeest, Amsterdam, The Netherlands.
Institute of Education and Child Studies, Forensic Family and Youth Care, Leiden University, Leiden, The Netherlands.
Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
Institute of Medical Imaging & Visualisation, Faculty of Health & Social Sciences, Bournemouth University, Bournemouth, UK.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
Imaging Diagnostic Center, Hospital Clínic, Barcelona, Spain.
Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
Department for Clinical Psychology, Würzburg University, Margetshöchheim, Germany.
Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
Department of Psychiatry, University of Basel, Basel, Switzerland.
Department of Psychiatry, University of Lübeck, Lübeck, Germany.
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Alzheimer Center, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Neuroscience Centre Zurich, University and ETH Zurich, Zurich, Switzerland.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Dementia Centre for Research Collaboration, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.
Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Atlanta, Georgia, USA.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, New York, USA.
Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Psychology Clinical Neuroscience Center, Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA.
Mind Research Network, Albuquerque, New Mexico, USA.
Department of Psychiatry, University of Montreal, Montreal, Canada.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Tübingen, Tübingen, Germany.
Department of Psychology (Clinical Psychology II), PFH - Private University of Applied Sciences, Göttingen, Germany.
Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, Bordeaux, France.
Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia.
Orygen, Parkville, Victoria, Australia.
Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Division of Psychological & Social Medicine and Developmental Neurosciences; Technische Universität Dresden, Faculty of Medicine, University Hospital C.G. Carus, Dresden, Germany.
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Tommy Fuss Center for Neuropsychiatric Disease Research, Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Olin Center for Neuropsychiatric Research, Institute of Living, Hartford Hospital, Hartford, Connecticut, USA.
Department of Psychology, Stanford University, Stanford, California, USA.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
Lifespan Brain Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Early Psychosis, Amsterdam UMC, Amsterdam, The Netherlands.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia.
Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
Departments of Experimental and Clinical Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Psychology, Yale University, New Haven, Connecticut, USA.
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa.
De Bascule, Academic center child and adolescent psychiatry, Duivendrecht, The Netherlands.
Amsterdam UMC Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
Department of Psychiatry, Warneford Hospital, Oxford, UK.
Highfield Unit, Warneford Hospital, Oxford, UK.
Department of Radiology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Department of Psychology, University of Oslo, Oslo, Norway.
Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
Sunshine Coast Mind and Neuroscience Thompson Institute, Birtinya, Queensland, Australia.
University of the Sunshine Coast, Sunshine Coast, Queensland, Australia.
Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic, Barcelona, Spain.
August Pi i Sunyer Biomedical Research Institut (IDIBAPS), Barcelona, Spain.
Department of Medicine, University of Barcelona, Barcelona, Spain.
Laboratory of Neuroimaging and Multimodal Analysis, Mental Health Research Center, Moscow, Russia.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, Western Cape, South Africa.
Department of Psychiatry, Academic Medical Center, Amsterdam, The Netherlands.
Institut des maladies neurodégénératives, Université de Bordeaux, Bordeaux, France.
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.
Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
University of Bordeaux, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Herston Imaging Research Facility and School of Clinical Sciences, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Department of Radiation Sciences, Umeå University, Umeå, Sweden.
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Emma Children's Hospital, Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
Clinical Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Psychology, University of Würzburg, Würzburg, Germany.
Centre of Mental Health, Medical Faculty, University of Würzburg, Würzburg, Germany.
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Mary Land, USA.
Department of Psychiatry, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfur am Maint, Germany.
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, New South Wales, Australia.
Indiana Alzheimer Disease Center, Indianapolis, Indiana, USA.
West Region, Institute of Mental Health, Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neurology, King's College London, London, UK.
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Biomedical Sciences of Cells and Systems, Rijksuniversiteit Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, New York, New York, USA.
Department of Child and Adolescent Psychiatry and Psychotherapy, Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany.
Department of Psychiatry and Psychotherapy CCM, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Department of Psychiatry & Amsterdam Neuroscience, Amsterdam UMC, location VUMC, Amsterdam, The Netherlands.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
DZD (German Center for Diabetes Research), partner site Greifswald, Greifswald, Germany.
Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Institute for Experimental Epileptology and Cognition Research, University Hospital Bonn, Bonn, Germany.
Division of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK.
Department of Neuroimaging, King's College London, London, UK.
Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia.
Department of Child and Adolescent Psychiatry, NYU Child Study Center, Hassenfeld Children's Hospital at NYU Langone, New York, New York, USA.
Instituto de Ensino e Pesquisa, Hospital Sírio-Libanês, São Paulo, Brazil.
Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
Department of Psychology, Education and Child Studies (DPECS), Erasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam, The Netherlands.
Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

中文翻译：

整个生命周期中，男性区域大脑结构的变异性大于女性

对于许多特征来说，男性比女性表现出更大的变异性，这可能对理解健康和疾病方面的性别差异产生影响。在这里，ENIGMA（通过荟萃分析增强神经影像遗传学）联盟基于跨越九个十年生命的国际数据，对大脑结构变异性的性别差异进行了有史以来最大规模的大型分析。通过 16,683 名 1-90 岁健康个体（47% 为女性）的 MRI 数据评估皮质下体积、皮质表面积和皮质厚度。我们观察到，在所有皮层下体积测量、所有皮层表面积测量和 60% 的皮层厚度测量中，男性受试者间方差大于女性。对于 50% 的皮层下结构、70% 的区域面积测量以及几乎所有区域的厚度，这种模式在整个生命周期中都是稳定的。我们的研究结果表明，这些性别差异存在于童年时期，这与早期生命的遗传或基因-环境相互作用机制有关。研究结果强调了性别内个体差异的重要性，这可能会导致特定性别对疾病的脆弱性。

更新日期：2020-10-12

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