Dataset Information

Genome-Wide Association Study of Latent Cognitive Measures in Adolescence: Genetic Overlap With Intelligence and Education.

ABSTRACT: Individual differences in executive functions (EF) are heritable and predictive of academic attainment (AA). However, little is known about genetic contributions to EFs or their genetic relationship with AA and intelligence. We conducted genome-wide association analyses for processing speed (PS) and the latent EF measures of working memory (WM) and inhibitory control (IC) in 4,611 adolescents from the Avon Longitudinal Study of Parents and Children. While no loci reached genome-wide significance, common genetic variants explained 30% of the variance in WM and 19% in PS. In contrast, we failed to find common genetic contributions to IC. Finally, we examined shared genetic effects between EFs and general intelligence, AA and ADHD. We identified significant genetic correlations between WM, intelligence, and AA. A more specific pattern was observed for PS, with modest genetic overlap with intelligence. Together these findings highlight diversity in the genetic contributions to specific cognitive functions and their genetic relationship with educational and psychiatric outcomes.

SUBMITTER: Donati G

PROVIDER: S-EPMC6771723 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of Latent Cognitive Measures in Adolescence: Genetic Overlap With Intelligence and Education.

Donati Georgina G Dumontheil Iroise I Meaburn Emma L EL

Mind, brain and education : the official journal of the International Mind, Brain, and Education Society 20190630 3

Individual differences in executive functions (EF) are heritable and predictive of academic attainment (AA). However, little is known about genetic contributions to EFs or their genetic relationship with AA and intelligence. We conducted genome-wide association analyses for processing speed (PS) and the latent EF measures of working memory (WM) and inhibitory control (IC) in 4,611 adolescents from the Avon Longitudinal Study of Parents and Children. While no loci reached genome-wide significance ...[more]

PMID: 31598132

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Project description:BACKGROUND:Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. METHODS:A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999-2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency > or = 0.10, genotypic call rate > or = 0.80, and Hardy-Weinberg equilibrium p-value > or = 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. RESULTS:The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 x 10(-6)) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 x 10(-8)) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). CONCLUSION:Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.

Dataset Information

Genome-Wide Association Study of Latent Cognitive Measures in Adolescence: Genetic Overlap With Intelligence and Education.

Publications

Genome-Wide Association Study of Latent Cognitive Measures in Adolescence: Genetic Overlap With Intelligence and Education.

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