Age at first birth in women is genetically associated with increased risk of schizophrenia

被引：0

作者：

Guiyan Ni

Jacob Gratten

Naomi R. Wray

Sang Hong Lee

机构：

[1] University of South Australia,Australian Center for Precision Health, University of South Australia Cancer Research Institute

[2] University of New England,School of Environmental and Rural Science

[3] University of Queensland,Institute for Molecular Bioscience

[4] University of Queensland,Queensland Brain Institute

[5] Massachusetts General Hospital,Analytic and Translational Genetics Unit

[6] Broad Institute of MIT and Harvard,Stanley Center for Psychiatric Research

[7] Broad Institute of MIT and Harvard,Medical and Population Genetics Program

[8] Massachusetts General Hospital,Psychiatric and Neurodevelopmental Genetics Unit

[9] Trinity College Dublin,Neuropsychiatric Genetics Research Group, Department of Psychiatry

[10] Cardiff University,MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine

[11] Cardiff University,National Centre for Mental Health

[12] Erl Wood Manor,Eli Lilly and Company Limited

[13] King’s College London,Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry

[14] Technical University of Denmark,Center for Biological Sequence Analysis, Department of Systems Biology

[15] Boston Children’s Hospital,Division of Endocrinology and Center for Basic and Translational Obesity Research

[16] Boston,Department of Clinical Neuroscience, Psychiatry Section

[17] Karolinska Institutet,Department of Psychiatry

[18] Diakonhjemmet Hospital,NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine

[19] University of Oslo,Centre for Integrative Register

[20] Aarhus University,based Research, CIRRAU

[21] AarhusUniversity,National Centre for Register

[22] iPSYCH,based Research

[23] State Mental Hospital,The Lundbeck Foundation Initiative for Integrative Psychiatric Research

[24] Stanford University,Department of Psychiatry and Behavioral Sciences

[25] Atlanta Veterans Affairs Medical Center,Department of Psychiatry and Behavioral Sciences

[26] Emory University,Department of Psychiatry and Behavioral Sciences

[27] Virginia Commonwealth University,Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry

[28] Max Planck Institute of Experimental Medicine,Clinical Neuroscience

[29] University of Pécs,Department of Medical Genetics

[30] University of Pécs,Szentagothai Research Center

[31] Karolinska Institutet,Department of Medical Epidemiology and Biostatistics

[32] University of Iowa Carver College of Medicine,Department of Psychiatry

[33] University Medical Center Groningen,School of Nursing

[34] Department of Psychiatry,Athinoula A Martinos Center

[35] University of Groningen,Center for Brain Science

[36] Louisiana State University Health Sciences Center,Department of Psychiatry

[37] Massachusetts General Hospital,Department of Psychiatry

[38] Harvard University,Department of Human Genetics

[39] Massachusetts General Hospital,Department of Psychiatry

[40] University of California at San Francisco,Department of Human Genetics, David Geffen School of Medicine

[41] University Medical Center Utrecht,School of Psychiatry

[42] Department of Psychiatry,Royal Brisbane and Women’s Hospital

[43] Rudolf Magnus Institute of Neuroscience,Institute of Psychology

[44] Icahn School of Medicine at Mount Sinai,Department of Psychiatry, Li Ka Shing Faculty of Medicine

[45] Icahn School of Medicine at Mount Sinai,State Key Laboratory for Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine

[46] Centre Hospitalier du Rouvray and INSERM U1079 Faculty of Medicine,Department of Computer Science

[47] University of California,Department of Psychiatry

[48] Schizophrenia Research Institute,Department of Child and Adolescent Psychiatry, Assistance Publique Hopitaux de Paris

[49] University of New South Wales,Department of Genetics

[50] University of Queensland,Department of Psychological Medicine

来源：

Scientific Reports | / 8卷

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摘要：

Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is −0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.

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