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A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence
S L Spain1, I Pedroso1, N Kadeva1
1Department of Medical and Molecular Genetics, Division of Genetics and Molecular Medicine, King's College London, London, UK.
Molecular Psychiatry
|August 5, 2015
Summary
This study found no specific gene variants linked to extremely high intelligence (IQ >170). However, genetic variations explain about 17.4% of intelligence heritability, suggesting rare gene variants may be detrimental.
Area of Science:
- Genetics
- Cognitive Neuroscience
- Behavioral Genetics
Background:
- Intelligence (general cognitive ability) is highly heritable, but specific genetic factors remain largely unidentified.
- Previous molecular genetic studies have had limited success in pinpointing loci responsible for intelligence heritability.
- Investigating exome variation in individuals with extremely high intelligence offers increased power to detect genetic associations.
Purpose of the Study:
- To identify specific exonic variants associated with extremely high intelligence (IQ >170).
- To estimate the heritability attributable to genotyped functional protein-altering variation.
- To test the hypothesis that rare functional alleles are detrimental to intelligence.
Main Methods:
- Case-control association analysis comparing 1409 individuals with IQ >170 against 3253 population-based controls.
- Focus on putative functional exonic variants using the Illumina HumanExome BeadChip.
- Genome-wide complex trait analysis (GCTA) to estimate heritability from shared genetic variation.
Main Results:
- No individual protein-altering variants were reproducibly associated with extremely high intelligence or overall intelligence.
- No significant associations were found for multiple rare alleles within individual genes.
- Genome-wide complex trait analysis estimated that genotyped functional variation accounts for 17.4% (s.e. 1.7%) of intelligence heritability.
- Fewer rare alleles were associated with extremely high intelligence than expected by chance, supporting a detrimental role for rare functional alleles.
Conclusions:
- Specific exonic variants do not appear to be major contributors to extremely high intelligence.
- Genotyped functional variation contributes significantly to the heritability of intelligence.
- Rare functional alleles may more frequently negatively impact intelligence than positively influence it.
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