8 research outputs found
Genetic associations with childhood brain growth, defined in two longitudinal cohorts
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 Ă 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
Type I error rates of rare single nucleotide variants are inflated in tests of association with nonânormally distributed traits using simple linear regression methods
Plasma Levels of Soluble Interleukin-2 Receptor αSignificance: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan
Interleukin-2 receptor subunit alpha (IL-2Rα) regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels
Genomeâwide association study of cafĂ©âauâlait macule number in neurofibromatosis type 1
Abstract Background Neurofibromatosis type 1 (NF1) is a tumorâpredisposition disorder that arises due to pathogenic variants in tumor suppressor NF1. NF1 has variable expressivity that may be due, at least in part, from heritable elements such as modifier genes; however, few genetic modifiers have been identified to date. Methods In this study, we performed a genomeâwide association analysis of the number of cafĂ©âauâlait macules (CALM) that are considered a tumorâlike trait as a clinical phenotype modifying NF1. Results A borderline genomeâwide significant association was identified in the discovery cohort (CALM1, N = 112) between CALM number and rs12190451 (and rs3799603, r2 = 1.0; p = 7.4 Ă 10â8) in the intronic region of RPS6KA2. Although, this association was not replicated in the second cohort (CALM2, N = 59) and a metaâanalysis did not show significantly associated variants in this region, a significant corroboration score (0.72) was obtained for the RPS6KA2 signal in the discovery cohort (CALM1) using Complementary Pairs Stability Selection for GenomeâWide Association Studies (ComPaSSâGWAS) analysis, suggesting that the lack of replication may be due to heterogeneity of the cohorts rather than type I error. Conclusion rs12190451 is located in a melanocyteâspecific enhancer and may influence RPS6KA2 expression in melanocytesâwarranting further functional studies