Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controlsDepartment of Psychiatry, Washington University in Saint Louis School of Medicine, Saint Louis, MO, USA.
Department of Biomedicine, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Analytic and Translational Genetics Unit (ATGU), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Department of Medicine, Division of Genetic Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biomedicine, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
Indiana University School of Medicine, Biochemistry and Molecular Biology, Indianapolis, IN, USA; Indiana University School of Medicine, Medical and Molecular Genetics, Indianapolis, IN, USA.
Department of Biomedicine, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark; BiRC-Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
Yale University School of Medicine, Genetics and Neurobiology, New Haven, CT, USA; US Department of Veterans Affairs, Psychiatry, West Haven, CT, USA; Yale University School of Medicine, Psychiatry, New Haven, CT, USA.
Analytic and Translational Genetics Unit (ATGU), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales.
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, Wales, UK.
Analytic and Translational Genetics Unit (ATGU), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands; Department of Clinical Genetics, VU University Medical Center (VUMC), Amsterdam, The Netherlands.
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands.
Show others and affiliations
2019 (English)In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 49, no 7, p. 1166-1173Article in journal (Refereed) Published
Abstract [en]
BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
RESULTS: Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
CONCLUSIONS: Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Place, publisher, year, edition, pages
Cambridge University Press, 2019. Vol. 49, no 7, p. 1166-1173
Keywords [en]
ADHD, alcohol dependence, anorexia nervosa, autism spectrum disorders, bipolar disorder, genes, heritability, major depressive disorder, obsessive compulsive disorder, schizophrenia
National Category
Psychiatry Psychology
Identifiers
URN: urn:nbn:se:oru:diva-71743DOI: 10.1017/S0033291718002039ISI: 000474921600011PubMedID: 30221610Scopus ID: 2-s2.0-85053674930OAI: oai:DiVA.org:oru-71743DiVA, id: diva2:1281861
Funder
Wellcome trust, WT 088827/Z/09
Note
Funding Agencies:
Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) 340-2013-5867
NIMH U01 MH109528
UK Medical Research Council MR/L010305/1 MR/L011794/1
Lundbeck Foundation R102-A9118 R155-2014-1724
Stanley Medical Research Institute
European Research Council 294838
Aarhus University
Netherlands Organization for Scientific Research NWO VICI 453-14-005
NIMH NIH HHS U01 MH109536 U01 MH109532 U01 MH109528
Medical Research Council MR/L010305/1
2019-01-232019-01-232019-11-15Bibliographically approved