Skip to main content Accessibility help

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 (a1), P. Lichtenstein (a1), H. Larsson (a1) (a2), J. Song (a1), 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 (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a8) (a9) (a10) (a11) (a12) (a13) (a14) (a15) (a16) (a17) (a18) (a19) (a20) (a21) (a22), A. Agrawal (a3), A. D. Børglum (a4) (a5) (a6), C. M. Bulik (a1) (a7), M. J. Daly (a8) (a9) (a10), L. K. Davis (a11), D. Demontis (a4) (a5) (a6), H. J. Edenberg (a12) (a13), J. Grove (a4) (a5) (a6) (a14), J. Gelernter (a15) (a16) (a17), B. M. Neale (a8) (a9) (a10), A. F. Pardiñas (a18), E. Stahl (a19), J. T. R. Walters (a18), R. Walters (a8) (a10), P. F. Sullivan (a1) (a20), D. Posthuma (a21) (a22) and T. J. C. Polderman (a21)...
  • Please note a correction has been issued for this article.



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.


This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Author for correspondence: Tinca Polderman, E-mail:


Hide All
Altman, DG and Bland, JM (2003) Interaction revisited: the difference between two estimates. BMJ (Clinical research ed.) 326, 219.
Bulik-Sullivan, BK, Loh, P-R, Finucane, HK, Ripke, S, Yang, J, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Patterson, N, Daly, MJ, Price, AL and Neale, BM (2015) LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics 47, 291295.
CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium, Psychosis Endophenotypes International Consortium (2017) Contribution of copy number variants to schizophrenia from a genome-wide study of 41 321 subjects. Nature Genetics 49, 2735.
Colvert, E, Tick, B, McEwen, F, Stewart, C, Curran, SR, Woodhouse, E, Gillan, N, Hallett, V, Lietz, S, Garnett, T, Ronald, A, Plomin, R, Rijsdijk, F, Happé, F and Bolton, P (2015) Heritability of autism spectrum disorder in a UK population-based twin sample. JAMA Psychiatry 72, 415423.
Demontis, D, Walters, RK, Martin, J, Mattheisen, M, Als, TD, Agerbo, E, Belliveau, R, Bybjerg-Grauholm, J, Bækved-Hansen, M, Cerrato, F, Chambert, K, Churchhouse, C, Dumont, A, Eriksson, N, Gandal, M, Goldstein, J, Grove, J, Hansen, CS, Hauberg, M, Hollegaard, M, Howrigan, DP, Huang, H, Maller, J, Martin, AR, Moran, J, Pallesen, J, Palmer, DS, Pedersen, CB, Pedersen, MG, Poterba, T, Poulsen, JB, Ripke, S, Robinson, EB, Satterstrom, FK, Stevens, C, Turley, P, Won, H, Con -ADHD Working Group of the Psychiatric Genomics, Lifecourse & -Early, Epidemiology (EAGLE) G, Team −23 and Me Research, Andreassen, OA, Burton, C, Boomsma, D, Cormand, B, Dalsgaard, S, Franke, B, Gelernter, J, Geschwind, D, Hakonarson, H, Haavik, J, Kranzler, H, Kuntsi, J, Langley, K, Lesch, K-P, Middeldorp, C, Reif, A, Rohde, LA, Roussos, P, Schachar, R, Sklar, P, Sonuga-Barke, E, Sullivan, PF, Thapar, A, Tung, J, Waldman, I, Nordentoft, M, Hougaard, DM, Werge, T, Mors, O, Mortensen, PB, Daly, MJ, Faraone, SV, Børglum, AD and Neale, BM (2017) Discovery of the first genome-wide significant risk loci for ADHD. Submitted for publication, bioRxiv. 2017; 14558:143.
Eaton, WW, Martins, SS, Nestadt, G, Bienvenu, OJ, Clarke, D and Alexandre, P (2008) The burden of mental disorders. Epidemiologic Reviews 30, 114.
Evans, LM, Tahmasbi, R, Vrieze, SI, Abecasis, GR, Das, S, Gazal, S, Bjelland, DW, de Candia, TR, Haplotype Reference Consortium, Goddard, ME, Neale, BM, Yang, J, Visscher, PM and Keller, MC (2018) Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits. Nature Genetics 50, 737745.
Hiroi, N, Takahashi, T, Hishimoto, A, Izumi, T, Boku, S and Hiramoto, T (2013) Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders. Molecular Psychiatry 18, 11531165.
Kendler, KS, Thornton, LM and Pedersen, NL (2000) Tobacco consumption in Swedish twins reared apart and reared together. Archives of General Psychiatry 57, 886892.
Lubke, GH, Hudziak, JJ, Derks, EM, van Bijsterveldt, TCEM and Boomsma, DI (2009) Maternal ratings of attention problems in ADHD: evidence for the existence of a continuum. Journal of the American Academy of Child and Adolescent Psychiatry 48, 10851093.
Mazzeo, SE, Mitchell, KS, Bulik, CM, Reichborn-Kjennerud, T, Kendler, KS and Neale, MC (2009) Assessing the heritability of anorexia nervosa symptoms using a marginal maximal likelihood approach. Psychological Medicine 39, 463473.
Moffitt, TE, Caspi, A, Taylor, A, Kokaua, J, Milne, BJ, Polanczyk, G and Poulton, R (2010) How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment. Psychological Medicine 40, 899909.
Mullins, N, Power, RA, Fisher, HL, Hanscombe, KB, Euesden, J, Iniesta, R, Levinson, DF, Weissman, MM, Potash, JB, Shi, J, Uher, R, Cohen-Woods, S, Rivera, M, Jones, L, Jones, I, Craddock, N, Owen, MJ, Korszun, A, Craig, IW, Farmer, AE, McGuffin, P, Breen, G and Lewis, CM (2016) Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychological Medicine 46, 759770.
Muthén, L.K. and Muthén, B.O. (1998) Mplus User's Guide, 7th Edn. Los Angeles, CA: Muthén & Muthén.
Nordsletten, AE, Larsson, H, Crowley, JJ, Almqvist, C, Lichtenstein, P and Mataix-Cols, D (2016) Patterns of nonrandom mating within and across 11 major psychiatric disorders. JAMA Psychiatry 73, 354361.
Petrou, S, Johnson, S, Wolke, D, Hollis, C, Kochhar, P and Marlow, N (2010) Economic costs and preference-based health-related quality of life outcomes associated with childhood psychiatric disorders. The British Journal of Psychiatry: The Journal of Mental Science 197, 395404.
Pettersson, E, Larsson, H and Lichtenstein, P (2016) Common psychiatric disorders share the same genetic origin: a multivariate sibling study of the Swedish population. Molecular Psychiatry 21, 717721.
Peyrot, WJ, Milaneschi, Y, Abdellaoui, A, Sullivan, PF, Hottenga, JJ, Boomsma, DI and Penninx, BWJH (2014) Effect of polygenic risk scores on depression in childhood trauma. The British Journal of Psychiatry: The Journal of Mental Science 205, 113119.
Peyrot, WJ, Boomsma, DI, Penninx, BWJH and Wray, NR (2016 a). Disease and polygenic architecture: avoid trio design and appropriately account for unscreened control subjects for common disease. American Journal of Human Genetics 98, 382391.
Peyrot, WJ, Robinson, MR, Penninx, BWJH and Wray, NR (2016 b). Exploring boundaries for the genetic consequences of assortative mating for psychiatric traits. JAMA Psychiatry 73, 11891195.
Peyrot, WJ, Van der Auwera, S, Milaneschi, Y, Dolan, CV, Madden, PAF, Sullivan, PF, Strohmaier, J, Ripke, S, Rietschel, M, Nivard, MG, Mullins, N, Montgomery, GW, Henders, AK, Heat, AC, Fisher, HL, Dunn, EC, Byrne, EM, Air, TA, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Baune, BT, Breen, G, Levinson, DF, Lewis, CM, Martin, NG, Nelson, EN, Boomsma, DI, Grabe, HJ, Wray, NR and Penninx, BWJH (2017) Does childhood trauma moderate polygenic risk for depression? A meta-analysis of 5765 subjects from the psychiatric genomics consortium. Biological Psychiatry 84, 138147.
Polderman, TJC, Benyamin, B, de Leeuw, CA, Sullivan, PF, van Bochoven, A, Visscher, PM and Posthuma, D (2015) Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics 47, 702709.
Psychiatric GWAS Consortium Coordinating Committee, Cichon, S, Craddock, N, Daly, M, Faraone, SV, Gejman, PV, Kelsoe, J, Lehner, T, Levinson, DF, Moran, A, Sklar, P and Sullivan, PF (2009) Genomewide association studies: history, rationale, and prospects for psychiatric disorders. The American Journal of Psychiatry 166, 540556.
Psychiatric GWAS Consortium Steering Committee (2009) A framework for interpreting genome-wide association studies of psychiatric disorders. Molecular Psychiatry 14, 1017.
Rietveld, MJH, Hudziak, JJ, Bartels, M, van Beijsterveldt, CEM and Boomsma, DI (2004) Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12. Journal of Child Psychology and Psychiatry, and Allied Disciplines 45, 577588.
Rokholm, B, Silventoinen, K, Tynelius, P, Gamborg, M, Sørensen, TIA and Rasmussen, F (2011) Increasing genetic variance of body mass index during the Swedish obesity epidemic. PloS ONE 6, e27135.
Sanders, SJ, He, X, Willsey, AJ, Ercan-Sencicek, AG, Samocha, KE, Cicek, AE, Murtha, MT, Bal, VH, Bishop, SL, Dong, S, Goldberg, AP, Jinlu, C, Keaney, JF, Klei, L, Mandell, JD, Moreno-De-Luca, D, Poultney, CS, Robinson, EB, Smith, L, Solli-Nowlan, T, Su, MY, Teran, NA, Walker, MF, Werling, DM, Beaudet, AL, Cantor, RM, Fombonne, E, Geschwind, DH, Grice, DE, Lord, C, Lowe, JK, Mane, SM, Martin, DM, Morrow, EM, Talkowski, ME, Sutcliffe, JS, Walsh, CA, Yu, TW, Autism Sequencing Consortium, Ledbetter, DH, Martin, CL, Cook, EH, Buxbaum, JD, Daly, MJ, Devlin, B, Roeder, K and State, MW (2015) Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 12151233.
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.
Sundquist, J, Ohlsson, H, Sundquist, K and Kendler, KS (2017) Common adult psychiatric disorders in Swedish primary care where most mental health patients are treated. BMC Psychiatry 17, 235.
Thomas, R, Sanders, S, Doust, J, Beller, E and Glasziou, P (2015) Prevalence of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Pediatrics 135, e994e1001.
Uher, R and Zwicker, A (2017) Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness. World Psychiatry: Official Journal of the World Psychiatric Association (WPA) 16, 121129.
Van Naarden Braun, K, Christensen, D, Doernberg, N, Schieve, L, Rice, C, Wiggins, L, Schendel, D and Yeargin-Allsopp, M (2015) Trends in the prevalence of autism spectrum disorder, cerebral palsy, hearing loss, intellectual disability, and vision impairment, metropolitan Atlanta, 1991-2010. PloS ONE 10, e0124120.
Vinkhuyzen, AAE, Wray, NR, Yang, J, Goddard, ME and Visscher, PM (2013) Estimation and partition of heritability in human populations using whole-genome analysis methods. Annual Review of Genetics 47, 7595.
Visscher, PM, Goddard, ME, Derks, EM and Wray, NR (2012) Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses. Molecular Psychiatry 17, 474485.
Warrier, V, Grasby, KL, Uzefovsky, F, Toro, R, Smith, P, Chakrabarti, B, Khadake, J, Mawbey-Adamson, E, Litterman, N, Hottenga, J-J, Lubke, G, Boomsma, DI, Martin, NG, Hatemi, PK, Medland, SE, Hinds, DA, Bourgeron, T and Baron-Cohen, S (2017) Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition. Molecular Psychiatry 23, 14021409.
Williams, NM, Zaharieva, I, Martin, A, Langley, K, Mantripragada, K, Fossdal, R, Stefansson, H, Stefansson, K, Magnusson, P, Gudmundsson, OO, Gustafsson, O, Holmans, P, Owen, MJ, O'Donovan, M and Thapar, A (2010) Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376, 14011408.
Wray, NR and Maier, R (2014) Genetic basis of Complex genetic disease: the contribution of disease heterogeneity to missing heritability. Current Epidemiology Reports 1, 220227.
Yang, J, Zeng, J, Goddard, ME, Wray, NR and Visscher, PM (2017) Concepts, estimation and interpretation of SNP-based heritability. Nature Genetics 49, 13041310.
Zablotsky, B, Black, LI, Maenner, MJ, Schieve, LA and Blumberg, SJ (2015) Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 national health interview survey. National Health Statistics Reports 13, 120.
Zavos, HMS, Freeman, D, Haworth, CMA, McGuire, P, Plomin, R, Cardno, AG and Ronald, A (2014) Consistent etiology of severe, frequent psychotic experiences and milder, less frequent manifestations: a twin study of specific psychotic experiences in adolescence. JAMA Psychiatry 71, 10491057.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Pettersson et al. supplementary material
Pettersson et al. supplementary material 1

 Word (360 KB)
360 KB
Supplementary materials

Pettersson et al. supplementary material
Pettersson et al. supplementary material 2

 Word (65 KB)
65 KB
Supplementary materials

Pettersson et al. supplementary material
Pettersson et al. supplementary material 3

 Unknown (12 KB)
12 KB
Supplementary materials

Pettersson et al. supplementary material
Pettersson et al. supplementary material 4

 Unknown (44 KB)
44 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed