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

Neumann A, Nolte IM, Pappa I, Ahluwalia TS, Pettersson E, Rodriguez A, Whitehouse A, van Beijsterveldt CEM, Benyamin B, Hammerschlag AR, Helmer Q, Karhunen V, Krapohl E, Lu Y, van der Most PJ, Palviainen T, St Pourcain B, Seppälä I, Suarez A, Vilor-Tejedor N, Tiesler CMT, Wang C, Wills A, Zhou A, Alemany S, Bisgaard H, Bønnelykke K, Davies GE, Hakulinen C, Henders AK, Hyppönen E, Stokholm J, Bartels M, Hottenga JJ, Heinrich J, Hewitt J, Keltikangas-Järvinen L, Korhonen T, Kaprio J, Lahti J, Lahti-Pulkkinen M, Lehtimäki T, Middeldorp CM, Najman JM, Pennell C, Power C, Oldehinkel AJ, Plomin R, Räikkönen K, Raitakari OT, Rimfeld K, Sass L, Snieder H, Standl M, Sunyer J, Williams GM, Bakermans-Kranenburg MJ, Boomsma DI, van IJzendoorn MH, Hartman CA, Tiemeier H

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.

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Reference

Neumann A, Nolte IM, Pappa I, Ahluwalia TS, Pettersson E, Rodriguez A, Whitehouse A, van Beijsterveldt CEM, Benyamin B, Hammerschlag AR, Helmer Q, Karhunen V, Krapohl E, Lu Y, van der Most PJ, Palviainen T, St Pourcain B, Seppälä I, Suarez A, Vilor-Tejedor N, Tiesler CMT, Wang C, Wills A, Zhou A, Alemany S, Bisgaard H, Bønnelykke K, Davies GE, Hakulinen C, Henders AK, Hyppönen E, Stokholm J, Bartels M, Hottenga JJ, Heinrich J, Hewitt J, Keltikangas-Järvinen L, Korhonen T, Kaprio J, Lahti J, Lahti-Pulkkinen M, Lehtimäki T, Middeldorp CM, Najman JM, Pennell C, Power C, Oldehinkel AJ, Plomin R, Räikkönen K, Raitakari OT, Rimfeld K, Sass L, Snieder H, Standl M, Sunyer J, Williams GM, Bakermans-Kranenburg MJ, Boomsma DI, van IJzendoorn MH, Hartman CA, Tiemeier H. A genome-wide association study of total child psychiatric problems scores. PLoS One. 2022 Aug 22;17(8):e0273116. doi: 10.1371/journal.pone.0273116. PMID: 35994476; PMCID: PMC9394806.