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. 2019 May;49(7):1166-1173.
doi: 10.1017/S0033291718002039. Epub 2018 Sep 17.

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

E Pettersson  1 , P Lichtenstein  1 , H Larsson  1 , J Song  1 ; Attention Deficit/Hyperactivity Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Autism Spectrum Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Bipolar Disorder Working Group of the PGC, Eating Disorder Working Group of the PGC, Major Depressive Disorder Working Group of the PGC, Obsessive Compulsive Disorders and Tourette Syndrome Working Group of the PGC, Schizophrenia CLOZUK, Substance Use Disorder Working Group of the PGC; A Agrawal  2 , A D Børglum  3 , C M Bulik  1 , M J Daly  4 , L K Davis  5 , D Demontis  3 , H J Edenberg  6 , J Grove  3 , J Gelernter  7 , B M Neale  4 , A F Pardiñas  8 , E Stahl  9 , J T R Walters  8 , R Walters  4 , P F Sullivan  1 , D Posthuma  10 , T J C Polderman  10
Affiliations

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

E Pettersson et al. Psychol Med. 2019 May.

Erratum in

  • 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 - CORRIGENDUM.
    Pettersson E, Lichtenstein P, Larsson H, Song J; Attention Deficit/Hyperactivity Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Autism Spectrum Disorder Working Group of the iPSYCH-Broad-PGC Consortium, Bipolar Disorder Working Group of the PGC, Eating Disorder Working Group of the PGC, Major Depressive Disorder Working Group of the PGC, Obsessive Compulsive Disorders and Tourette Syndrome Working Group of the PGC, Schizophrenia CLOZUK, Substance Use Disorder Working Group of the PGC; Agrawal A, Børglum AD, Bulik CM, Daly MJ, Davis LK, Demontis D, Edenberg HJ, Grove J, Gelernter J, Neale BM, Pardiñas AF, Stahl E, Walters JTR, Walters R, Sullivan PF, Posthuma D, Polderman TJC. Pettersson E, et al. Psychol Med. 2019 Jan;49(2):351. doi: 10.1017/S0033291718002945. Epub 2018 Oct 18. Psychol Med. 2019. PMID: 30334498 Free PMC article. No abstract available.

Abstract

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.

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

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Figures

Fig. 1.
Fig. 1.
h2-national and h2-SNP estimates ordered from low to high based on h2-national. Note: Error bars represent standard errors. AD, alcohol dependence; ADHD, attention deficit/hyperactivity disorder; AN, anorexia nervosa; ASD, autism spectrum disorder; BIP, bipolar disorder; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; SCZ, schizophrenia.
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