1. A genome-wide association study of total child psychiatric problems scores
- Author
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Carol A. Wang, Erik Pettersson, Jari Lahti, Irene Pappa, Gail M. Williams, Peter J. van der Most, Olli T. Raitakari, Jackob M. Najman, Henning Tiemeier, Amanda G. Wills, Craig E. Pennell, Terho Lehtimäki, Jouke-Jan Hottenga, Katri Räikkönen, Jakob Stokholm, Tarunveer S. Ahluwalia, Eva Krapohl, Marinus H. van IJzendoorn, Ilkka Seppälä, Christian Hakulinen, John K. Hewitt, Joachim Heinrich, Catharina E. M. van Beijsterveldt, Robert Plomin, Beben Benyamin, Marius Lahti-Pulkkinen, Lærke Sass, Ville Karhunen, Meike Bartels, Beate St Pourcain, Marie Standl, Silvia Alemany, Andrew J. O. Whitehouse, Alexander Neumann, Carla M. T. Tiesler, Gareth E. Davies, Elina Hyppönen, Catharina A. Hartman, Liisa Keltikangas-Järvinen, Ilja M. Nolte, Ang Zhou, Dorret I. Boomsma, Anjali K. Henders, Alina Rodriguez, Klaus Bønnelykke, Christel M. Middeldorp, Hans Bisgaard, Anke R. Hammerschlag, Kaili Rimfeld, Albertine J. Oldehinkel, Teemu Palviainen, Chris Power, Jaakko Kaprio, Tellervo Korhonen, Marian J. Bakermans-Kranenburg, Natalia Vilor-Tejedor, Yi Lu, Quinta Helmer, Anna Suarez, Jordi Sunyer, Harold Snieder, Neumann, Alexander [0000-0001-6653-3203], Ahluwalia, Tarunveer S [0000-0002-7464-3354], Rodriguez, Alina [0000-0003-1209-8802], van der Most, Peter J [0000-0001-8450-3518], Palviainen, Teemu [0000-0002-7847-8384], Kaprio, Jaakko [0000-0002-3716-2455], Lahti-Pulkkinen, Marius [0000-0002-5244-5525], Najman, Jackob M [0000-0001-7079-2080], Tiemeier, Henning [0000-0002-4395-1397], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Institute for Molecular Medicine Finland, Genetic Epidemiology, University of Helsinki, Developmental Psychology Research Group, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Faculty Common Matters (Faculty of Education), Psychosocial factors and health, Medicum, Tellervo Korhonen / Principal Investigator, Department of Public Health, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Clinical Child and Family Studies, LEARN! - Child rearing, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S, Benyamin, Beben, Zhou, Ang, Hyppönen, Elina, and Tiemeier, Henning
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Bipolar Disorder ,Genome-wide association study ,Expression ,Quality-control ,Genome-wide association studies ,genome-wide ,0302 clinical medicine ,Human genetics ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,Bipolar Disorder/genetics ,1184 Genetics, developmental biology, physiology ,Single Nucleotide ,Metaanalysis ,Neuroticism ,3. Good health ,Physical sciences ,Eating disorders ,psychiatric disorders ,Schizophrenia ,Genome-Wide Association Study/methods ,Anxiety ,medicine.symptom ,Attention Deficit Disorder with Hyperactivity/genetics ,Research Article ,medicine.medical_specialty ,General psychopathology factor ,General Science & Technology ,Genetic loci ,Population ,FOS: Physical sciences ,Polymorphism, Single Nucleotide ,Age-of-onset ,Heritability ,03 medical and health sciences ,children ,medicine ,ADHD ,Humans ,Genetic Predisposition to Disease ,Clinical genetics ,Bipolar disorder ,Polymorphism ,Psychiatry ,education ,childhood ,030304 developmental biology ,Medicine and health sciences ,Biology and life sciences ,business.industry ,Questionnaire ,Single nucleotide polymorphisms ,medicine.disease ,Research and analysis methods ,Attention-deficit/hyperactivity disorder ,Attention Deficit Disorder with Hyperactivity ,Symptoms ,Autism ,Gene expression ,Human medicine ,3111 Biomedicine ,business ,030217 neurology & neurosurgery ,Model ,Genome-Wide Association Study - 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. The work of H. Tiemeier is further supported by a European Union’s Horizon 2020 research and innovation program (Contract grant number: 633595, DynaHealth) and a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). https://www.nwo.nl/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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- 2022
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