TY - JOUR
T1 - A genome-wide association study of total child psychiatric problems scores
AU - Neumann, Alexander
AU - Nolte, Ilja M
AU - Pappa, Irene
AU - Ahluwalia, Tarunveer S
AU - Pettersson, Erik
AU - Rodriguez, Alina
AU - Whitehouse, Andrew
AU - van Beijsterveldt, Catharina E M
AU - Benyamin, Beben
AU - Hammerschlag, Anke R
AU - Helmer, Quinta
AU - Karhunen, Ville
AU - Krapohl, Eva
AU - Lu, Yi
AU - van der Most, Peter J
AU - Palviainen, Teemu
AU - St Pourcain, Beate
AU - Seppälä, Ilkka
AU - Suarez, Anna
AU - Vilor-Tejedor, Natalia
AU - Tiesler, Carla M T
AU - Wang, Carol
AU - Wills, Amanda
AU - Zhou, Ang
AU - Alemany, Silvia
AU - Bisgaard, Hans
AU - Bønnelykke, Klaus
AU - Davies, Gareth E
AU - Hakulinen, Christian
AU - Henders, Anjali K
AU - Hyppönen, Elina
AU - Stokholm, Jakob
AU - Bartels, Meike
AU - Hottenga, Jouke-Jan
AU - Heinrich, Joachim
AU - Hewitt, John
AU - Keltikangas-Järvinen, Liisa
AU - Korhonen, Tellervo
AU - Kaprio, Jaakko
AU - Lahti, Jari
AU - Lahti-Pulkkinen, Marius
AU - Lehtimäki, Terho
AU - Middeldorp, Christel M
AU - Najman, Jackob M
AU - Pennell, Craig
AU - Power, Chris
AU - Oldehinkel, Albertine J
AU - Plomin, Robert
AU - Räikkönen, Katri
AU - Raitakari, Olli T
AU - Rimfeld, Kaili
AU - Sass, Lærke
AU - Snieder, Harold
AU - Standl, Marie
AU - Sunyer, Jordi
AU - Williams, Gail M
AU - Bakermans-Kranenburg, Marian J
AU - Boomsma, Dorret I
AU - van IJzendoorn, Marinus H
AU - Hartman, Catharina A
AU - Tiemeier, Henning
PY - 2022/8/22
Y1 - 2022/8/22
N2 - 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.
AB - 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.
KW - Attention Deficit Disorder with Hyperactivity/genetics
KW - Bipolar Disorder/genetics
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study/methods
KW - Humans
KW - Polymorphism, Single Nucleotide
U2 - 10.1371/journal.pone.0273116
DO - 10.1371/journal.pone.0273116
M3 - Article
C2 - 35994476
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0273116
ER -