Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder


  • Demontis D.
  • Walters R.K.
  • Rajagopal V.M.
  • Waldman I.D.
  • Grove J.
  • Als T.D.
  • Dalsgaard S.
  • Ribasas M.
  • Bybjerg-Grauholm J.
  • Bækvad-Hansen M.
  • Werge T.
  • Nordentoft M.
  • Mors O.
  • Mortensen P.B.
  • Andreassen O.A.
  • Arranz M.J.
  • Banaschewski T.
  • Bau C.
  • Bellgrove M.
  • Biederman J.
  • Brikell I.
  • Buitelaar J.K.
  • Burton C.L.
  • Casas M.
  • Crosbie J.
  • Doyle A.E.
  • Ebstein R.P.
  • Elia J.
  • Elizabeth C.C.
  • Grevet E.
  • Grizenko N.
  • Havdahl A.
  • Hawi Z.
  • Hebebrand J.
  • Hervas A.
  • Hohmann S.
  • Haavik J.
  • Joober R.
  • Kent L.
  • Kuntsi J.
  • Langley K.
  • Larsson H.
  • Lesch K.P.
  • Leung P.W.L.
  • Liao C.
  • Loo S.K.
  • Martin J.
  • Martin N.G.
  • Medland S.E.
  • Miranda A.
  • Mota N.R.
  • Oades R.D.
  • Ramos-Quiroga J.A.
  • Reif A.
  • Rietschel M.
  • Roeyers H.
  • Rohde L.A.
  • Rothenberger A.
  • Rovira P.
  • Sánchez-Mora C.
  • Schachar R.J.
  • Sengupta S.
  • Artigas M.S.
  • Steinhausen H.C.
  • Thapar A.
  • Witt S.H.
  • Yang L.
  • Zayats T.
  • Zhang-James Y.
  • Cormand B.
  • Hougaard D.M.
  • Neale B.M.
  • Franke B.
  • Faraone S.V.
  • Børglum A.D.
Дата публикации:01.12.2021
Журнал: Nature Communications
БД: Scopus
Ссылка: Scopus

Аннтотация

© 2021, The Author(s). Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.


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