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The total burden of rare, non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

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    Rights statement: &2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.

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Original languageEnglish
Article number20140117
Number of pages7
JournalProceedings of the Royal Society B-Biological Sciences
Issue number1781
Publication statusPublished - 22 Apr 2014


Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation-selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/ loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability.

    Research areas

  • genetic burden, exome, general cognitive ability, intelligence, fitness, mutation-selection balance, HUMAN INTELLIGENCE, GENERAL INTELLIGENCE, MENTAL-DISORDERS, MATE PREFERENCES, AGE, MUTATIONS, STABILITY, INTEGRITY, DECLINE, DISEASE

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