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Genome-wide association studies establish that human intelligence is highly heritable and polygenic.

ABSTRACT: General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549,692 single nucleotide polymorphisms (SNPs) and detailed phenotypes on cognitive traits. We estimate that 40% of the variation in crystallized-type intelligence and 51% of the variation in fluid-type intelligence between individuals is accounted for by linkage disequilibrium between genotyped common SNP markers and unknown causal variants. These estimates provide lower bounds for the narrow-sense heritability of the traits. We partitioned genetic variation on individual chromosomes and found that, on average, longer chromosomes explain more variation. Finally, using just SNP data we predicted ?1% of the variance of crystallized and fluid cognitive phenotypes in an independent sample (P=0.009 and 0.028, respectively). Our results unequivocally confirm that a substantial proportion of individual differences in human intelligence is due to genetic variation, and are consistent with many genes of small effects underlying the additive genetic influences on intelligence.

SUBMITTER: Davies G

PROVIDER: S-EPMC3182557 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association studies establish that human intelligence is highly heritable and polygenic.

Davies G G Tenesa A A Payton A A Yang J J Harris S E SE Liewald D D Ke X X Le Hellard S S Christoforou A A Luciano M M McGhee K K Lopez L L Gow A J AJ Corley J J Redmond P P Fox H C HC Haggarty P P Whalley L J LJ McNeill G G Goddard M E ME Espeseth T T Lundervold A J AJ Reinvang I I Pickles A A Steen V M VM Ollier W W Porteous D J DJ Horan M M Starr J M JM Pendleton N N Visscher P M PM Deary I J IJ

Molecular psychiatry 20110809 10

General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated ...[more]

PMID: 21826061

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Project description:IMPORTANCE:Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES:To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS:Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES:Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS:A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P?=?9.26?×?10-9 in the discovery meta-analysis). This association was not replicated (P?=?.32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P?=?2.38?×?10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09?×?10-12?<?P?<?.05) and MDD (4.02?×?10-9?<?P?<?.05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE:This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

Dataset Information

Genome-wide association studies establish that human intelligence is highly heritable and polygenic.

Publications

Genome-wide association studies establish that human intelligence is highly heritable and polygenic.

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