Genetic association study of childhood aggression across raters, instruments, and age

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Ip , H F , van der Laan , C M , Krapohl , E M L , Brikell , I , Sanchez-Mora , C , Nolte , I M , St Pourcain , B , Bolhuis , K , Palviainen , T , Zafarmand , H , Colodro-Conde , L , Gordon , S , Zayats , T , Aliev , F , Jiang , C , Wang , C A , Saunders , G , Karhunen , V , Hammerschlag , A R , Adkins , D E , Border , R , Peterson , R E , Prinz , J A , Thiering , E , Seppala , I , Vilor-Tejedor , N , Ahluwalia , T S , Day , F R , Hottenga , J-J , Allegrini , A G , Rimfeld , K , Chen , Q , Lu , Y , Martin , J , Soler Artigas , M , Rovira , P , Bosch , R , Espanol , G , Ramos Quiroga , J A , Neumann , A , Ensink , J , Grasby , K , Morosoli , J J , Tong , X , Marrington , S , Middeldorp , C , Scott , J G , Vinkhuyzen , A , Shabalin , A A , Corley , R , Evans , L M , Sugden , K , Alemany , S , Sass , L , Vinding , R , Ruth , K , Tyrrell , J , Davies , G E , Ehli , E A , Hagenbeek , F A , De Zeeuw , E , Van Beijsterveldt , T C E M , Larsson , H , Snieder , H , Verhulst , F C , Amin , N , Whipp , A M , Korhonen , T , Vuoksimaa , E , Rose , R J , Uitterlinden , A G , Heath , A C , Madden , P , Haavik , J , Harris , J R , Helgeland , O , Johansson , S , Knudsen , G P S , Njolstad , P R , Lu , Q , Rodriguez , A , Henders , A K , Mamun , A , Najman , J M , Brown , S , Hopfer , C , Krauter , K , Reynolds , C , Smolen , A , Stallings , M , Wadsworth , S , Wall , T L , Silberg , J L , Miller , A , Keltikangas-Järvinen , L , Hakulinen , C , Pulkki-Råback , L , Havdahl , A , Magnus , P , Raitakari , O T , Perry , J R B , Llop , S , Lopez-Espinosa , M-J , Bonnelykke , K , Bisgaard , H , Sunyer , J , Lehtimaki , T , Arseneault , L , Standl , M , Heinrich , J , Boden , J , Pearson , J , Horwood , L J , Kennedy , M , Poulton , R , Eaves , L J , Maes , H H , Hewitt , J , Copeland , W E , Costello , E J , Williams , G M , Wray , N , Jarvelin , M-R , McGue , M , Iacono , W , Caspi , A , Moffitt , T E , Whitehouse , A , Pennell , C E , Klump , K L , Burt , S A , Dick , D M , Reichborn-Kjennerud , T , Martin , N G , Medland , S E , Vrijkotte , T , Kaprio , J , Tiemeier , H , Davey Smith , G , Hartman , C A , Oldehinkel , A J , Casas , M , Ribases , M , Lichtenstein , P , Lundstrom , S , Plomin , R , Bartels , M , Nivard , M G & Boomsma , D I 2021 , ' Genetic association study of childhood aggression across raters, instruments, and age ' , Translational Psychiatry , vol. 11 , no. 1 , 413 . https://doi.org/10.1038/s41398-021-01480-x

Title: Genetic association study of childhood aggression across raters, instruments, and age
Author: Ip, Hill F.; van der Laan, Camiel M.; Krapohl, Eva M. L.; Brikell, Isabell; Sanchez-Mora, Cristina; Nolte, Ilja M.; St Pourcain, Beate; Bolhuis, Koen; Palviainen, Teemu; Zafarmand, Hadi; Colodro-Conde, Lucia; Gordon, Scott; Zayats, Tetyana; Aliev, Fazil; Jiang, Chang; Wang, Carol A.; Saunders, Gretchen; Karhunen, Ville; Hammerschlag, Anke R.; Adkins, Daniel E.; Border, Richard; Peterson, Roseann E.; Prinz, Joseph A.; Thiering, Elisabeth; Seppala, Ilkka; Vilor-Tejedor, Natalia; Ahluwalia, Tarunveer S.; Day, Felix R.; Hottenga, Jouke-Jan; Allegrini, Andrea G.; Rimfeld, Kaili; Chen, Qi; Lu, Yi; Martin, Joanna; Soler Artigas, Maria; Rovira, Paula; Bosch, Rosa; Espanol, Gemma; Ramos Quiroga, Josep Antoni; Neumann, Alexander; Ensink, Judith; Grasby, Katrina; Morosoli, Jose J.; Tong, Xiaoran; Marrington, Shelby; Middeldorp, Christel; Scott, James G.; Vinkhuyzen, Anna; Shabalin, Andrey A.; Corley, Robin; Evans, Luke M.; Sugden, Karen; Alemany, Silvia; Sass, Laerke; Vinding, Rebecca; Ruth, Kate; Tyrrell, Jess; Davies, Gareth E.; Ehli, Erik A.; Hagenbeek, Fiona A.; De Zeeuw, Eveline; Van Beijsterveldt, Toos C. E. M.; Larsson, Henrik; Snieder, Harold; Verhulst, Frank C.; Amin, Najaf; Whipp, Alyce M.; Korhonen, Tellervo; Vuoksimaa, Eero; Rose, Richard J.; Uitterlinden, Andre G.; Heath, Andrew C.; Madden, Pamela; Haavik, Jan; Harris, Jennifer R.; Helgeland, Oyvind; Johansson, Stefan; Knudsen, Gun Peggy S.; Njolstad, Pal Rasmus; Lu, Qing; Rodriguez, Alina; Henders, Anjali K.; Mamun, Abdullah; Najman, Jackob M.; Brown, Sandy; Hopfer, Christian; Krauter, Kenneth; Reynolds, Chandra; Smolen, Andrew; Stallings, Michael; Wadsworth, Sally; Wall, Tamara L.; Silberg, Judy L.; Miller, Allison; Keltikangas-Järvinen, Liisa; Hakulinen, Christian; Pulkki-Råback, Laura; Havdahl, Alexandra; Magnus, Per; Raitakari, Olli T.; Perry, John R. B.; Llop, Sabrina; Lopez-Espinosa, Maria-Jose; Bonnelykke, Klaus; Bisgaard, Hans; Sunyer, Jordi; Lehtimaki, Terho; Arseneault, Louise; Standl, Marie; Heinrich, Joachim; Boden, Joseph; Pearson, John; Horwood, L. John; Kennedy, Martin; Poulton, Richie; Eaves, Lindon J.; Maes, Hermine H.; Hewitt, John; Copeland, William E.; Costello, Elizabeth J.; Williams, Gail M.; Wray, Naomi; Jarvelin, Marjo-Riitta; McGue, Matt; Iacono, William; Caspi, Avshalom; Moffitt, Terrie E.; Whitehouse, Andrew; Pennell, Craig E.; Klump, Kelly L.; Burt, S. Alexandra; Dick, Danielle M.; Reichborn-Kjennerud, Ted; Martin, Nicholas G.; Medland, Sarah E.; Vrijkotte, Tanja; Kaprio, Jaakko; Tiemeier, Henning; Davey Smith, George; Hartman, Catharina A.; Oldehinkel, Albertine J.; Casas, Miquel; Ribases, Marta; Lichtenstein, Paul; Lundstrom, Sebastian; Plomin, Robert; Bartels, Meike; Nivard, Michel G.; Boomsma, Dorret I.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Genetic Epidemiology
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Cognitive and Brain Aging
University of Helsinki, Medicum
University of Helsinki, Helsinki Inequality Initiative (INEQ)
University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2021-07-30
Language: eng
Number of pages: 9
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
URI: http://hdl.handle.net/10138/334429
Abstract: Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
Subject: GENOME-WIDE ASSOCIATION
TRAJECTORIES
HERITABILITY
ADOLESCENCE
DISORDER
BEHAVIOR
ORIGINS
3124 Neurology and psychiatry
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