Dataset Information

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

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.

SUBMITTER: Ritchie SJ

PROVIDER: S-EPMC4082597 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Ritchie Stuart J SJ Bates Timothy C TC Corley Janie J McNeill Geraldine G Davies Gail G Liewald David C DC Starr John M JM Deary Ian J IJ

Age (Dordrecht, Netherlands) 20140321 3

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 alco ...[more]

PMID: 24652602

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Project description:Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers' development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127-3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306-17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer.

Dataset Information

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

Publications

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

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