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Psychol Med. 2018 Sep 17:1-8. doi: 10.1017/S0033291718002039. [Epub ahead of print]

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 controls.

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Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
Department of Psychiatry,Washington University in Saint Louis School of Medicine,Saint Louis, MO,USA.
Department of Biomedicine,Aarhus University,Aarhus,Denmark.
Analytic and Translational Genetics Unit (ATGU), Department of Medicine,Massachusetts General Hospital and Harvard Medical School,Boston, Massachusetts,USA.
Department of Medicine, Division of Genetic Medicine,Vanderbilt Genetics Institute, Vanderbilt University Medical Center,Nashville, TN,USA.
Indiana University School of Medicine, Biochemistry and Molecular Biology,Indianapolis, IN,USA.
Yale University School of Medicine, Genetics and Neurobiology,New Haven, CT,USA.
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University,Cardiff, Wales.
Division of Psychiatric Genomics,Icahn School of Medicine at Mount Sinai,New York, NY,USA.
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.



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.


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.


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.


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.


ADHD; alcohol dependence; anorexia nervosa; autism spectrum disorders; bipolar disorder; genes; heritability; major depressive disorder; obsessive compulsive disorder; schizophrenia


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