Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

Howard, D. M. et al. (2017) Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank. Wellcome Open Research, 2, 61. (doi: 10.12688/wellcomeopenres.12171.1) (PMID:28989979) (PMCID:PMC5605947)

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Abstract

Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7), was the butyrylcholinesterase (BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lyall, Dr Donald
Authors: Howard, D. M., Adams, M. J., Clarke, T.-K., Wigmore, E. M., Zeng, Y., Hagenaars, S. P., Lyall, D. M., Thomson, P. A., Evans, K. L., Porteous, D. J., Nagy, R., Hayward, C., Haley, C. S., Smith, B. H., Murray, A. D., Batty, G. D., Deary, I. J., and McIntosh, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Wellcome Open Research
Publisher:F1000Research
ISSN:2398-502X
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Wellcome Open Research 2: 61
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381721Generation ScotlandAnna DominiczakChief Scientist office (CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES