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A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Martin J, Walters RK, Mattheisen M, Lee SH, Brikell I, Ghirardi L, Larsson H, Lichtenstein P, Eriksson N, Agee M, Alipanahi B, Auton A, Bell RK, Bryc K, Elson SL, Fontanillas P, Furlotte NA, Hinds DA, Hromatka BS, Huber KE, Kleinman A, Litterman NK, McIntyre MH, Mountain JL, Northover CA, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Tung JY, Vacic V, Wilson CH, Albayrak Ö, Anney RJ, Vasquez AA, Arranz MJ, Asherson P, Banaschewski TJ, Bau C, Biederman J, Mortensen PB, Buitelaar JK, Casas M, Charach A, Cormand B, Crosbie J, Dalsgaard S, Daly MJ, Dempfle A, Doyle AE, Ebstein RP, Elia J, Faraone SV, Föcker M, Franke B, Freitag C, Gelernter J, Gill M, Grevet E, Haavik J, Hakonarson H, Hawi Z, Hebebrand J, Herpertz-Dahlmann B, Hervas A, Hinney A, Hohmann S, Holmans P, Hutz M, Ickowitz A, Johansson S, Kent L, Kittel-Schneider S, Kranzler H, Kuntsi J, Lambregts-Rommelse N, Langley K, Lehmkuhl G, Lesch KP, Loo SK, McGough JJ, Medland SE, Meyer J, Mick E, Middletion F, Miranda A, Mulas F, Mulligan A, Neale BM, Nelson SF, Nguyen TT, O'Donovan MC, Oades RD, Owen MJ, Palmason H, Ramos-Quiroga JA, Reif A, Renner TJ, Rhode L, Ribasés M, Rietschel M, Ripke S, Rivero O, Roeyers H, Romanos M, Romanos J, Mota NR, Rothenberger A, Sánchez-Mora C, Schachar R, Schäfer H, Scherag A, Schimmelmann BG, Sergeant J, Sinzig J, Smalley SL, Sonuga-Barke EJ, Steinhausen HC, Sullivan PF, Thapar A, Thompsom M, Todorov A, Waldman I, Walitza S, Wang Y, Warnke A, Williams N, Witt SH, Yang L, Zayats T, Zhang-James Y, Agerbo E, Als TD, Bækved-Hansen M, Belliveau R, Bybjerg-Grauholm J, Cerrato F, Chambert K, Churchhouse C, Demontis D, Dumont A, Goldstein J, Grove J, Hansen CS, Hauberg ME, Hollegaard MV, Hougaard DM, Howrigan DP, Huang H, Maller J, Martin AR, Martin J, Moran J, Mors O, Nordentoft M, Pallesen J, Palmer DS, Pedersen CB, Pedersen MG, Poterba T, Poulsen JB, Robinson EB, Satterstrom FK, Stevens C, Turley P, Werge T, Wray NR, Børglum AD (2018)

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Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 83

Pages Range: 1044-1053

Journal Issue: 12

DOI: 10.1016/j.biopsych.2017.11.026

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Results: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98–1.06], p =.28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11–1.18], p = 1.5E-15). Conclusions: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.

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How to cite

APA:

Martin, J., Walters, R.K., Mattheisen, M., Lee, S.H., Brikell, I., Ghirardi, L.,... Børglum, A.D. (2018). A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 83(12), 1044-1053. https://doi.org/10.1016/j.biopsych.2017.11.026

MLA:

Martin, Joanna, et al. "A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder." Biological Psychiatry 83.12 (2018): 1044-1053.

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