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:Combining information from multiple SNPs may capture a greater amount of genetic variation than from the sum of individual SNP effects and help identifying missing heritability. Regions may capture variation from multiple common variants of small effect, multiple rare variants or a combination of both. We describe regional heritability mapping of human cognition. Measures of crystallised (gc) and fluid intelligence (gf) in late adulthood (64-79 years) were available for 1806 individuals genotyped for 549,692 autosomal single nucleotide polymorphisms (SNPs). The same individuals were tested at age 11, enabling us the rare opportunity to measure cognitive change across most of their lifespan. 547,750 SNPs ranked by position are divided into 10, 908 overlapping regions of 101 SNPs to estimate the genetic variance each region explains, an approach that resembles classical linkage methods. We also estimate the genetic variation explained by individual autosomes and by SNPs within genes. Empirical significance thresholds are estimated separately for each trait from whole genome scans of 500 permutated data sets. The 5% significance threshold for the likelihood ratio test of a single region ranged from 17-17.5 for the three traits. This is the equivalent to nominal significance under the expectation of a chi-squared distribution (between 1 df and 0) of P<1.44×10(-5). These thresholds indicate that the distribution of the likelihood ratio test from this type of variance component analysis should be estimated empirically. Furthermore, we show that estimates of variation explained by these regions can be grossly overestimated. After applying permutation thresholds, a region for gf on chromosome 5 spanning the PRRC1 gene is significant at a genome-wide 10% empirical threshold. Analysis of gene methylation on the temporal cortex provides support for the association of PRRC1 and fluid intelligence (P = 0.004), and provides a prime candidate gene for high throughput sequencing of these uniquely informative cohorts.

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.

Similar Datasets

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