Alcohol consumption and lifetime change in cognitive ability: a gene × environment interaction study - PubMed (original) (raw)

Randomized Controlled Trial

Alcohol consumption and lifetime change in cognitive ability: a gene × environment interaction study

Stuart J Ritchie et al. Age (Dordr). 2014 Jun.

Abstract

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Theoretical model of alcohol’s effect on lifetime cognitive change. SNPs causing differences in alcohol metabolism interact with the alcohol consumption: Those with few rare alleles (and a corresponding higher rate of alcohol metabolism) have lower biological exposure to damaging effects of alcohol and thus a relative IQ improvement from alcohol consumption. The opposite effect occurs in those with many rare alleles, resulting in relative IQ decline. Variables inside the dashed box were not directly measured in the present study

Fig. 2

Fig. 2

Histogram of four-SNP set scores (total number of rare/minor alleles from rs2866151, rs975833, rs4147536, and rs284779)

Fig. 3

Fig. 3

Lifetime cognitive change (age ∼70 cognitive ability adjusted for age ∼11 cognitive ability and confounders) against alcohol consumption, split by SNP set score quartile (quartiles are for illustration; note that analysis was performed on a continuous SNP score). Higher scores on the _y_-axis indicate better cognitive ability later in life. Higher SNP set scores indicate a greater number of rare alleles

References

    1. Anstey KJ, Mack HA, Cherbuin N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatr. 2009;17(7):542–555. doi: 10.1097/JGP.0b013e3181a2fd07. - DOI - PubMed
    1. Au Yeung SL, Jiang CQ, Cheng KK, Liu B, Zhang WS, Lam TH, Leung GM, Schooling CM. Evaluation of moderate alcohol use and cognitive function among men using a Mendelian randomization design in the Guangzhou Biobank Cohort Study. Am J Epidemiol. 2012;175(10):1021–1028. doi: 10.1093/aje/kwr462. - DOI - PubMed
    1. Birley AJ, James MR, Dickson PA, Montgomery GW, Heath AC, Martin NG, Whitfield JB. ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. Hum Mol Genet. 2009;18(8):1533–1542. doi: 10.1093/hmg/ddp060. - DOI - PMC - PubMed
    1. Brennan P, Lewis S, Hashibe M, Bell DA, Boffetta P, Bouchardy C, Caporaso N, Chen C, Coutelle C, Diehl SR, Hayes RB, Olshan AF, Schwartz SM, Sturgis EM, Wei Q, Zavras AI, Benhamou S. Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review. Am J Epidemiol. 2004;159(1):1–16. doi: 10.1093/aje/kwh003. - DOI - PubMed
    1. Brennan PL, Schutte KK, Moos BS, Moos RH. Twenty-year alcohol-consumption and drinking-problem trajectories of older men and women. J Stud Alcohol Drugs. 2011;72(2):308–321. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources