Genetic association study of childhood aggression across raters, instruments, and age
Adkins Daniel E.; Ahluwalia Tarunveer S.; Alemany Silvia; Aliev Fazil; Allegrini Andrea G.; Amin Najaf; Arseneault Louise; Artigas María Soler; Bartels Meike; Bisgaard Hans; Boden Joseph; Bolhuis Koen; Border Richard; Bosch Rosa; Brikell Isabell; Brown Sandy; Burt S. Alexandra; Bønnelykke Klaus; Casas Miquel; Caspi Avshalom; Chen Qi; Colodro-Conde Lucía; Copeland William E.; Corley Robin; Costello Elizabeth J.; Davies Gareth E.; Day Felix R.; De Zeeuw Eveline; Dick Danielle M.; Eaves Lindon J.; Ehli Erik A.; Ensink Judith; Español Gemma; Evans Luke M.; Gordon Scott; Grasby Katrina; Haavik Jan; Hagenbeek Fiona A.; Hakulinen Christian; Hammerschlag Anke R.; Harris Jennifer R.; Hartman Catharina A.; Havdahl Alexandra; Heath Andrew C.; Heinrich Joachim; Helgeland Øyvind; Henders Anjali K.; Hewitt John; Hopfer Christian; Horwood L. John; Hottenga Jouke-Jan; Iacono William; Ip Hill F.; Jiang Chang; Johansson Stefan; Järvelin Marjo-Riitta; Kaprio Jaakko; Karhunen Ville; Keltikangas-Järvinen Liisa; Kennedy Martin; Klump Kelly L.; Knudsen Gun Peggy S.; Korhonen Tellervo; Krapohl Eva M. L.; Krauter Kenneth; Larsson Henrik; Lehtimäki Terho; Lichtenstein Paul; Llop Sabrina; Lopez-Espinosa Maria-Jose; Lu Qing; Lu Yi; Lundström Sebastian; Madden Pamela; Maes Hermine H.; Magnus Per; Mamun Abdullah; Marrington Shelby; Martin Joanna; Martin Nicholas G.; McGue Matt; Medland Sarah E.; Middeldorp Christel; Miller Allison; Moffitt Terrie E.; Morosoli José J.; Najman Jackob M.; Neumann Alexander; Nivard Michel G. Boomsma Dorret I.; Njolstad Pal Rasmus; Nolte Ilja M.; Oldehinkel Albertine J.; Palviainen Teemu; Pearson John; Pennell Craig E.; Perry John R. B.; Peterson Roseann E.; Plomin Robert; Poulton Richie; Prinz Joseph A.; Pulkki-Råback Laura; Quiroga Josep Antoni Ramos; Raitakari Olli T.; Reichborn-Kjennerud Ted; Reynolds Chandra; Ribasés Marta; Rimfeld Kaili; Rodriguez Alina; Rose Richard J.; Rovira Paula; Ruth Kate; Sass Lærke; Saunders Gretchen; Scott James G.; Seppälä Ilkka; Shabalin Andrey A.; Silberg Judy L.; Smith George Davey; Smolen Andrew; Snieder Harold; St Pourcain Beate; Stallings Michael; Standl Marie; Sugden Karen; Sunyer Jordi; Sánchez-Mora Cristina; Thiering Elisabeth; Tiemeier Henning; Tong Xiaoran; Tyrrell Jess; Uitterlinden André G.; Van Beijsterveldt Toos C.E.M.; Verhulst Frank C.; Vilor-Tejedor Natàlia; Vinding Rebecca; Vinkhuyzen Anna; Vrijkotte Tanja; Vuoksimaa Eero; Wadsworth Sally; Wall Tamara L.; Wang Carol A.; Whipp Alyce M.; Whitehouse Andrew; Williams Gail M.; Wray Naomi; Zafarmand Hadi; Zayats Tetyana; van der Laan Camiel M.
https://urn.fi/URN:NBN:fi-fe2021110253334
Tiivistelmä
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 AGGoverall. 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 rg= 0.46 between self- and teacher-assessment to rg= 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 |rg|: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg=∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 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.
Kokoelmat
- Rinnakkaistallenteet [19207]