Multivariate GWAMA in over 500K observations on aggressive behavior and ADHD symptoms

Abstract

We present the results of a multivariate genome-wide association (GWA) study of the developmental genetic etiology of aggressive behavior (AGG) and attention-deficit/hyperactivity disorder (ADHD). The project involves a... [ view full abstract ]

The cohorts are characterized by rich phenotyping in children and adolescents, including repeated measures at different ages and assessment by multiple informants and multiple instruments. In total, the meta-analysis included ~526,000 observations and over 250 GWA studies.

The data includes longitudinal measures of AGG and ADHD in children and adolescents aged 3 to 18 years, assessed by multiple informants (mother, father, teacher, and self) and multiple instruments. First, a series of univariate GWA studies was performed for every available combination of age, informant and instrument within cohort. This resulted in 1 to 52 analyses per cohort, with sample sizes ranging between 309 and 10,812. Next, results were pooled into age-by-informant combinations (e.g. mother-rated aged 3-5, teacher-rated 8-11, etc.) that resulted in an excess of 10,000 independent observations, and then meta-analyzed. Genetic correlations between the age-by-informant meta-analyses, both within and across AGG and ADHD, were estimated with LD Score Regression. We then performed a multivariate meta-regression analysis across all GWA studies, correcting for dependency due to repeated measurements of the participants.

We obtained an average SNP-heritability of 6.1% and 7.2% for AGG and ADHD, respectively, across the age-by-informant meta-analyses. After meta-analysis across age, genetic correlations between mother- and teacher-ratings was 0.54 for AGG and 0.51 for ADHD. Interestingly, the genetic correlation between teacher-ratings and self-report approached zero for both traits. Genetic correlation within rater, across phenotype ranged from 0.58 to 0.7. The multivariate meta-analysis across rater and phenotype revealed no significant loci for AGG/ADHD.

Our study includes multiple international cohorts (ABCD, Add Health, ALSPAC, BREATHE, CATSS, Dunedin Study, E-RISK, FINNTWIN, GENR, GINI/LISA, IBG, INMA, MOBA, MSUTR, MTFS, MUSP, NFBC 1966/1986, NTR, QIMR, RAINE, Richmond State University, TCHAD, TEDS, TRAILS, Understanding Society, YFS).

Authors

Hill Ip (Department of Biological Psychology, VU University)
Hadi Zafarmand (University of Amsterdam)
Robbee Wedow (University of Colorado Boulder, Institute for Behavioral Genetics)
Beate St. Pourcain (University of Bristol)
Silvia Alemany (Instituto de Salud Global Barcelona)
Natàlia Vilor-tejedor (Centre for Genomic Regulation)
Sebastian Lundström (University of Gothenburg)
Yi Lu (Karolinska Institutet)
Qi Chen (Department of Medical Epidemiology and Biostatistics, Karolinska Institute)
Isabell Brikell (Karolinska Institutet)
Joanna Martin (Cardiff University, Karolinska Institutet)
Karen Sugden (Duke Center for Genomic and Computational Biology)
Joseph Prinz (Duke Center for Genomic and Computational Biology)
Teemu Palviainen (University of Helsinki)
Anu Loukola (University of Helsinki)
Tellervo Korhonen (University of Helsinki)
Eero Vuoksimaa (University of Helsinki)
Alexander Neumann (The Generation R Study Group, Erasmus Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, the Netherlands)
Koen Bolhuis (The Generation R Study Group, Erasmus Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000 CA, the Netherlands)
Elisabeth Thiering (Helmholtz Zentrum München)
Marie Standl (Helmholtz Zentrum München)
Amanda Wills (University of Colorado Boulder, Institute for Behavioral Genetics)
Robin Corley (University of Colorado Boulder, Institute for Behavioral Genetics)
Richard Border (University of Colorado Boulder, Institute for Behavioral Genetics)
Sabrina Llop (Universitat de València)
Tetyana Zayats (Broad In)
Qing Lu (Michigan State University)
Gretchen Saunders (University of Minnesota, Twin Cities)
Anna Vinkhuyzen (Institute for Molecular Bioscience, The University of Queensland)
Anke R Hammerschlag (Department of Biological Psychology, VU University)
Ville Karhunen (Imperial College London)
Michel Nivard (Department of Biological Psychology, VU University)
Lucia Colodro Conde (QIMR-Berghofer Medical Research Institute)
Katrina Grasby (Queensland Institute of Medical Research)
José J Morosoli (Queensland Institute of Medical Research)
Carol Wang (School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle (UON), Australia)
Eva Krapohl (King's College London)
Catharina Hartman (Rijksuniversiteit Groningen)
Ilja Nolte (Universitair Medisch Centrum Groningen)
Ilkka Seppala (University of Tampere)
Christian Hakulinen (University of Helsinki)

Topic Area

Developmental Disorders (e.g. ADHD)

Session

SY-8B » Family and molecular genetic studies provide insights into ADHD, its comorbidities (Aggression and auto-immune disorders) and symptomatology (10:30 - Saturday, 23rd June, Yellowstone)

Paper

IP_BGA_2018_abstract_Final_Upload.pdf

Presentation Files

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