Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression
Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression
Abstract Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N=4,178, 65.5% female; mean age=41.5 years; N=1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age=45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.
Baune Bernhard T.、Martin Joanna、Asjadi Kimiya、Pardi?as Antonio F.、Hamilton Steven P.、Magnusson Patrik K.、McIntosh Andrew M.、Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium、Rice Frances、Rietschel Marcella、Hubbard Leon、Mors Ole、Walters James T. R.、Mullins Niamh、Lucae Susanne、O?ˉDonovan Michael、Penninx Brenda W. J. H.、Thapar Anita、Jermy Bradley、Kendall Kimberley、Jones Ian、Boomsma Dorret I.、Lewis Cathryn M.、Martin Nicholas G.、Mehta Divya、Preisig Martin
Department of Psychiatry, University of M¨1nster, M¨1nster||Department of Psychiatry, Melbourne Medical School, University of Melbourne||Florey Institute for Neuroscience and Mental Health, University of MelbourneMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityPsychiatry, Kaiser Permanente Northern CaliforniaDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDivision of Psychiatry, University of Edinburgh||Centre for Cognitive Ageing and Cognitive Epidemiology, University of EdinburghMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Psychosis Research Unit, Aarhus University HospitalMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University||National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversitySocial, Genetic and Developmental Psychiatry Centre, King?ˉs College London||Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Department of Psychiatry, Icahn School of Medicine at Mount SinaiMax Planck Institute of PsychiatryMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University||National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityDepartment of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeestMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University||National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversitySocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology& Neuroscience, King?ˉs College LondonMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityMRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University||National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityDept of Biological Psychology & EMGO+ Institute for Health and Care Research, Vrije Universiteit AmsterdamSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology& Neuroscience, King?ˉs College LondonGenetics and Computational Biology, QIMR Berghofer Medical Research InstituteQueensland University of Technology (QUT), Centre for Genomics and Personalised Health, Faculty of HealthDepartment of Psychiatry, Lausanne University Hospital and University of Lausanne
神经病学、精神病学医学研究方法基础医学
Baune Bernhard T.,Martin Joanna,Asjadi Kimiya,Pardi?as Antonio F.,Hamilton Steven P.,Magnusson Patrik K.,McIntosh Andrew M.,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,Rice Frances,Rietschel Marcella,Hubbard Leon,Mors Ole,Walters James T. R.,Mullins Niamh,Lucae Susanne,O?ˉDonovan Michael,Penninx Brenda W. J. H.,Thapar Anita,Jermy Bradley,Kendall Kimberley,Jones Ian,Boomsma Dorret I.,Lewis Cathryn M.,Martin Nicholas G.,Mehta Divya,Preisig Martin.Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression[EB/OL].(2025-03-28)[2025-04-29].https://www.medrxiv.org/content/10.1101/2021.02.22.21251925.点此复制
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