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Educational attainment: a genome wide association study in 9538 Australians.

ABSTRACT: Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ.In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of ?2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores.The best SNP fell short of having a genome-wide significant p-value (p?=?9.77×10(-7)). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r(2)<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing--rs7106258 (p?=?9.7*10(-4)) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample.While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA.

SUBMITTER: Martin NW

PROVIDER: S-EPMC3111411 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Educational attainment: a genome wide association study in 9538 Australians.

Martin Nicolas W NW Medland Sarah E SE Verweij Karin J H KJ Lee S Hong SH Nyholt Dale R DR Madden Pamela A PA Heath Andrew C AC Montgomery Grant W GW Wright Margaret J MJ Martin Nicholas G NG

PloS one 20110609 6

<h4>Background</h4>Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ.<h4>Methodology</h4>In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of ∼2.4 million single nucleotide ...[more]

PMID: 21694764

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Project description:Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Project description:Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance. To examine whether a childhood diagnosis of AD is associated with lower educational attainment. This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021. Hospital-diagnosed AD. Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age. The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]). This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.

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Educational attainment: a genome wide association study in 9538 Australians.

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Educational attainment: a genome wide association study in 9538 Australians.

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