A genome-wide association study of total child psychiatric problems scores

Author:

Neumann AlexanderORCID,Nolte Ilja M.,Pappa Irene,Ahluwalia Tarunveer S.ORCID,Pettersson Erik,Rodriguez AlinaORCID,Whitehouse Andrew,van Beijsterveldt Catharina E. M.,Benyamin Beben,Hammerschlag Anke R.,Helmer Quinta,Karhunen Ville,Krapohl Eva,Lu Yi,van der Most Peter J.ORCID,Palviainen TeemuORCID,St Pourcain Beate,Seppälä Ilkka,Suarez Anna,Vilor-Tejedor Natalia,Tiesler Carla M. T.,Wang Carol,Wills Amanda,Zhou Ang,Alemany Silvia,Bisgaard Hans,Bønnelykke Klaus,Davies Gareth E.,Hakulinen Christian,Henders Anjali K.,Hyppönen Elina,Stokholm Jakob,Bartels Meike,Hottenga Jouke-Jan,Heinrich Joachim,Hewitt John,Keltikangas-Järvinen Liisa,Korhonen Tellervo,Kaprio JaakkoORCID,Lahti Jari,Lahti-Pulkkinen MariusORCID,Lehtimäki Terho,Middeldorp Christel M.,Najman Jackob M.ORCID,Pennell Craig,Power Chris,Oldehinkel Albertine J.,Plomin Robert,Räikkönen Katri,Raitakari Olli T.,Rimfeld Kaili,Sass Lærke,Snieder Harold,Standl Marie,Sunyer Jordi,Williams Gail M.,Bakermans-Kranenburg Marian J.,Boomsma Dorret I.,van IJzendoorn Marinus H.,Hartman Catharina A.,Tiemeier HenningORCID

Abstract

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Funder

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Horizon 2020

ZonMw

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

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