Genetic associations with childhood brain growth,defined in two longitudinal cohorts |
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| Authors: | Eszter Szekely Tae‐ Hwi Linus Schwantes‐An Cristina M Justice Jeremy A Sabourin Philip R Jansen Ryan L Muetzel Wendy Sharp Henning Tiemeier Heejong Sung Tonya J White Alexander F Wilson Philip Shaw |
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| Affiliation: | 1. Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland, United States of America;2. Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Canada;3. Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, Baltimore, Maryland, United States of America;4. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America;5. The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands;6. Department of Child and Adolescent Psychiatry/Psychology, Sophia Children's Hospital—Erasmus Medical Center, Rotterdam, The Netherlands;7. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands |
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| Abstract: | Genome‐wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross‐sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome‐wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention‐deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population‐based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta‐analysis identified a genome‐wide significant intergenic SNP (rs12386571, P = 9.09 × 10?9), near AKR1B10. This gene is part of the aldo‐keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study. |
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| Keywords: | ADHD brain development children GWAS pathway analysis polygenic score |
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