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A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence

Year: 2015
Type: article
Study design: Observational Study
Abstract: Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.
DOI: 10.1038/mp.2015.108
Authors: S L Spain, I Pedroso, N Kadeva, M B Miller, W G Iacono, M McGue, E Stergiakouli, G D Smith, M Putallaz, D Lubinski, E L Meaburn, R Plomin, M A Simpson
Institutions: King's College London, University of Minnesota, University of Bristol, MRC Integrative Epidemiology Unit, Duke University, Vanderbilt University, University of London, Birkbeck, University of London
Language: English
Subfield: Genetics
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: John Templeton Foundation, Wellcome Trust, National Institutes of Health, U.S. Public Health Service, Medical Research Council, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse
Awards: G1104670545, G1342740831, Twin Study of Female Alcoholism and Other Disorders, Substance Abuse & Behavioral Disinhibition: Integrating Genes & Environment, G1971525463, G2399428660, G2584699021, G2761558319, Adolescent drinking and midlife outcomes: A prospective cotwin control study, G3935526752, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4590952238, The Avon Longitudinal Study of Parents and Children: An international resource for population genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, G5072599845, Twin Study of ADHD, CD and Substance Abuse, G5322692167, G5666390563, G6737906592, A Longitudinal Study of Adopted Youth and Their Families, Substance Abuse & Behavioral Disinhibition: Integrating Genes & Environment, Twin Family Study of Vulnerability to Substance Abuse, G7716769900, Adult consequences of youth substance use: Twin study enriched for SUD risk, Twin Family Study of Vulnerability to Substance Abuse, Sibling Models of Adolescent Alcohol Use and Abuse, G8882455512
OpenAlex ID: W1894235553
FWCI: 3.929
Cites: 54
Cited by: 33
Related to: 10