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

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 p...

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Main Authors: Alexander Neumann, Ilja M Nolte, Irene Pappa, Tarunveer S Ahluwalia, Erik Pettersson, Alina Rodriguez, Andrew Whitehouse, Catharina E M van Beijsterveldt, Beben Benyamin, Anke R Hammerschlag, Quinta Helmer, Ville Karhunen, Eva Krapohl, Yi Lu, Peter J van der Most, Teemu Palviainen, Beate St Pourcain, Ilkka Seppälä, Anna Suarez, Natalia Vilor-Tejedor, Carla M T Tiesler, Carol Wang, Amanda Wills, Ang Zhou, Silvia Alemany, Hans Bisgaard, Klaus Bønnelykke, Gareth E Davies, Christian Hakulinen, Anjali K Henders, Elina Hyppönen, Jakob Stokholm, Meike Bartels, Jouke-Jan Hottenga, Joachim Heinrich, John Hewitt, Liisa Keltikangas-Järvinen, Tellervo Korhonen, Jaakko Kaprio, Jari Lahti, Marius Lahti-Pulkkinen, Terho Lehtimäki, Christel M Middeldorp, Jackob M Najman, Craig Pennell, Chris Power, Albertine J Oldehinkel, Robert Plomin, Katri Räikkönen, Olli T Raitakari, Kaili Rimfeld, Lærke Sass, Harold Snieder, Marie Standl, Jordi Sunyer, Gail M Williams, Marian J Bakermans-Kranenburg, Dorret I Boomsma, Marinus H van IJzendoorn, Catharina A Hartman, Henning Tiemeier
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0273116
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author Alexander Neumann
Ilja M Nolte
Irene Pappa
Tarunveer S Ahluwalia
Erik Pettersson
Alina Rodriguez
Andrew Whitehouse
Catharina E M van Beijsterveldt
Beben Benyamin
Anke R Hammerschlag
Quinta Helmer
Ville Karhunen
Eva Krapohl
Yi Lu
Peter J van der Most
Teemu Palviainen
Beate St Pourcain
Ilkka Seppälä
Anna Suarez
Natalia Vilor-Tejedor
Carla M T Tiesler
Carol Wang
Amanda Wills
Ang Zhou
Silvia Alemany
Hans Bisgaard
Klaus Bønnelykke
Gareth E Davies
Christian Hakulinen
Anjali K Henders
Elina Hyppönen
Jakob Stokholm
Meike Bartels
Jouke-Jan Hottenga
Joachim Heinrich
John Hewitt
Liisa Keltikangas-Järvinen
Tellervo Korhonen
Jaakko Kaprio
Jari Lahti
Marius Lahti-Pulkkinen
Terho Lehtimäki
Christel M Middeldorp
Jackob M Najman
Craig Pennell
Chris Power
Albertine J Oldehinkel
Robert Plomin
Katri Räikkönen
Olli T Raitakari
Kaili Rimfeld
Lærke Sass
Harold Snieder
Marie Standl
Jordi Sunyer
Gail M Williams
Marian J Bakermans-Kranenburg
Dorret I Boomsma
Marinus H van IJzendoorn
Catharina A Hartman
Henning Tiemeier
author_facet Alexander Neumann
Ilja M Nolte
Irene Pappa
Tarunveer S Ahluwalia
Erik Pettersson
Alina Rodriguez
Andrew Whitehouse
Catharina E M van Beijsterveldt
Beben Benyamin
Anke R Hammerschlag
Quinta Helmer
Ville Karhunen
Eva Krapohl
Yi Lu
Peter J van der Most
Teemu Palviainen
Beate St Pourcain
Ilkka Seppälä
Anna Suarez
Natalia Vilor-Tejedor
Carla M T Tiesler
Carol Wang
Amanda Wills
Ang Zhou
Silvia Alemany
Hans Bisgaard
Klaus Bønnelykke
Gareth E Davies
Christian Hakulinen
Anjali K Henders
Elina Hyppönen
Jakob Stokholm
Meike Bartels
Jouke-Jan Hottenga
Joachim Heinrich
John Hewitt
Liisa Keltikangas-Järvinen
Tellervo Korhonen
Jaakko Kaprio
Jari Lahti
Marius Lahti-Pulkkinen
Terho Lehtimäki
Christel M Middeldorp
Jackob M Najman
Craig Pennell
Chris Power
Albertine J Oldehinkel
Robert Plomin
Katri Räikkönen
Olli T Raitakari
Kaili Rimfeld
Lærke Sass
Harold Snieder
Marie Standl
Jordi Sunyer
Gail M Williams
Marian J Bakermans-Kranenburg
Dorret I Boomsma
Marinus H van IJzendoorn
Catharina A Hartman
Henning Tiemeier
author_sort Alexander Neumann
collection DOAJ
description 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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spelling doaj-art-b496b6eb00a643ae88ae8e6c418358c32025-08-20T02:22:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027311610.1371/journal.pone.0273116A genome-wide association study of total child psychiatric problems scores.Alexander NeumannIlja M NolteIrene PappaTarunveer S AhluwaliaErik PetterssonAlina RodriguezAndrew WhitehouseCatharina E M van BeijsterveldtBeben BenyaminAnke R HammerschlagQuinta HelmerVille KarhunenEva KrapohlYi LuPeter J van der MostTeemu PalviainenBeate St PourcainIlkka SeppäläAnna SuarezNatalia Vilor-TejedorCarla M T TieslerCarol WangAmanda WillsAng ZhouSilvia AlemanyHans BisgaardKlaus BønnelykkeGareth E DaviesChristian HakulinenAnjali K HendersElina HyppönenJakob StokholmMeike BartelsJouke-Jan HottengaJoachim HeinrichJohn HewittLiisa Keltikangas-JärvinenTellervo KorhonenJaakko KaprioJari LahtiMarius Lahti-PulkkinenTerho LehtimäkiChristel M MiddeldorpJackob M NajmanCraig PennellChris PowerAlbertine J OldehinkelRobert PlominKatri RäikkönenOlli T RaitakariKaili RimfeldLærke SassHarold SniederMarie StandlJordi SunyerGail M WilliamsMarian J Bakermans-KranenburgDorret I BoomsmaMarinus H van IJzendoornCatharina A HartmanHenning TiemeierSubstantial 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.https://doi.org/10.1371/journal.pone.0273116
spellingShingle Alexander Neumann
Ilja M Nolte
Irene Pappa
Tarunveer S Ahluwalia
Erik Pettersson
Alina Rodriguez
Andrew Whitehouse
Catharina E M van Beijsterveldt
Beben Benyamin
Anke R Hammerschlag
Quinta Helmer
Ville Karhunen
Eva Krapohl
Yi Lu
Peter J van der Most
Teemu Palviainen
Beate St Pourcain
Ilkka Seppälä
Anna Suarez
Natalia Vilor-Tejedor
Carla M T Tiesler
Carol Wang
Amanda Wills
Ang Zhou
Silvia Alemany
Hans Bisgaard
Klaus Bønnelykke
Gareth E Davies
Christian Hakulinen
Anjali K Henders
Elina Hyppönen
Jakob Stokholm
Meike Bartels
Jouke-Jan Hottenga
Joachim Heinrich
John Hewitt
Liisa Keltikangas-Järvinen
Tellervo Korhonen
Jaakko Kaprio
Jari Lahti
Marius Lahti-Pulkkinen
Terho Lehtimäki
Christel M Middeldorp
Jackob M Najman
Craig Pennell
Chris Power
Albertine J Oldehinkel
Robert Plomin
Katri Räikkönen
Olli T Raitakari
Kaili Rimfeld
Lærke Sass
Harold Snieder
Marie Standl
Jordi Sunyer
Gail M Williams
Marian J Bakermans-Kranenburg
Dorret I Boomsma
Marinus H van IJzendoorn
Catharina A Hartman
Henning Tiemeier
A genome-wide association study of total child psychiatric problems scores.
PLoS ONE
title A genome-wide association study of total child psychiatric problems scores.
title_full A genome-wide association study of total child psychiatric problems scores.
title_fullStr A genome-wide association study of total child psychiatric problems scores.
title_full_unstemmed A genome-wide association study of total child psychiatric problems scores.
title_short A genome-wide association study of total child psychiatric problems scores.
title_sort genome wide association study of total child psychiatric problems scores
url https://doi.org/10.1371/journal.pone.0273116
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