Alcohol consumption and lifetime change in cognitive ability: a gene × environment interaction study.
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ABSTRACT:
SUBMITTER: Ritchie SJ
PROVIDER: S-EPMC4082597 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Previous genome-wide association studies (GWAS) have identified hundreds of genetic loci to be associated with body mass index (BMI) and risk of obesity. Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions. In this study, we examine gene-environment interactions in 362,496 unrelated participants with Caucasian ancestry from the UK Biobank resource. A total of 94 BMI-associated SNPs, selected from a previous GWAS on BMI, were used to construct weighted genetic scores for BMI (GSBMI). Linear regression modeling was used to estimate the effect of gene-environment interactions on BMI for 131 lifestyle factors related to: dietary habits, smoking and alcohol consumption, physical activity, socioeconomic status, mental health, sleeping patterns, as well as female-specific factors such as menopause and childbirth. In total, 15 lifestyle factors were observed to interact with GSBMI, of which alcohol intake frequency, usual walking pace, and Townsend deprivation index, a measure of socioeconomic status, were all highly significant (p = 1.45*10-29, p = 3.83*10-26, p = 4.66*10-11, respectively). Interestingly, the frequency of alcohol consumption, rather than the total weekly amount resulted in a significant interaction. The FTO locus was the strongest single locus interacting with any of the lifestyle factors. However, 13 significant interactions were also observed after omitting the FTO locus from the genetic score. Our analyses indicate that many lifestyle factors modify the genetic effects on BMI with some groups of individuals having more than double the effect of the genetic score. However, the underlying causal mechanisms of gene-environmental interactions are difficult to deduce from cross-sectional data alone and controlled experiments are required to fully characterise the causal factors.
| S-EPMC5600404 | biostudies-literature
Project description:To use Mendelian randomization to assess whether alcohol intake was causally associated with cognitive function.Mendelian randomization using a genetic variant related to alcohol intake (ADH1B rs1229984) was used to obtain unbiased estimates of the association between alcohol intake and cognitive performance.Europe.More than 34?000 adults.Any versus no alcohol intake and units of intake in the previous week was measured by questionnaire. Cognitive function was assessed in terms of immediate and delayed word recall, verbal fluency and processing speed.Having consumed any versus no alcohol was associated with higher scores by 0.17 standard deviations (SD) [95% confidence interval (CI)?=?0.15, 0.20] for immediate recall, 0.17 SD (95% CI?=?0.14, 0.19) for delayed recall, 0.17 SD (95% CI?=?0.14, 0.19) for verbal fluency and 0.12 SD (95% CI?=?0.09, 0.15) for processing speed. The minor allele of rs1229984 was associated with reduced odds of consuming any alcohol (odds ratio?=?0.87; 95% CI?=?0.80, 0.95; P?=?0.001; R(2) ?=?0.1%; F-statistic?=?47). In Mendelian randomization analysis, the minor allele was not associated with any cognitive test score, and instrumental variable analysis suggested no causal association between alcohol consumption and cognition: -0.74 SD (95% CI?=?-1.88, 0.41) for immediate recall, -1.09 SD (95% CI?=?-2.38, 0.21) for delayed recall, -0.63 SD (95% CI?=?-1.78, 0.53) for verbal fluency and -0.16 SD (95% CI?=?-1.29, 0.97) for processing speed.The Mendelian randomization analysis did not provide strong evidence of a causal association between alcohol consumption and cognitive ability.
| S-EPMC4309480 | biostudies-literature
Project description:Since 2005, a rapidly expanding literature has evaluated whether environmental factors such as socio-cultural context and adversity interact with genetic influences on drinking behaviors. This article critically reviews empirical research on alcohol-related genotype-environment interactions (GxE) and provides a contextual framework for understanding how genetic factors combine with (or are shaped by) environmental factors to influence the development of drinking behaviors and alcohol use disorders. Collectively, evidence from twin, adoption, and molecular genetic studies indicates that the degree of importance of genetic influences on risk for drinking outcomes can vary in different populations and under different environmental circumstances. However, methodological limitations and lack of consistent replications in this literature make it difficult to draw firm conclusions regarding the nature and effect size of alcohol-related GxE. On the basis of this review, we describe several methodological challenges as they relate to current research on GxE in drinking behaviors and provide recommendations to aid future research.
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Project description:Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a 'SNP set' composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data. We found two significant GE interactions for environmental measures in the home and the school both in the direction of the diathesis-stress type of GE interaction: The 10-SNP set was more strongly associated with mathematical ability in chaotic homes and when parents are negative.
| S-EPMC3029801 | biostudies-literature
Project description:BackgroundResults from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered.MethodsThe association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models.ResultsCompared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes.ConclusionsOur study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas.
| S-EPMC4559837 | biostudies-literature
Project description:ObjectivesMethamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons.MethodsEighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA-) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression.ResultsMA+ displayed moderately higher rates of impairment and lower T scores compared to MA-. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA-, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA- (b = -0.44, p = .030) but not MA+ (b = 0.08, p = .586).ConclusionsContrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.
| S-EPMC6733657 | biostudies-literature
Project description:ObjectiveTo determine whether alcohol consumption is causally associated with cognitive impairment in older men as predicted by mendelian randomization.MethodsRetrospective analysis of a cohort study of 3,542 community-dwelling men aged 65 to 83 years followed for 6 years. Cognitive impairment was established by a Mini-Mental State Examination score of 23 or less. Participants provided detailed information about their use of alcohol during the preceding year and were classified as abstainers, occasional drinkers, and regular drinkers: mild (<15 drinks/wk), moderate (15-27 drinks/wk), heavy (28-34 drinks/wk), and abusers (≥35 drinks/wk). We genotyped the rs1229984 G→A variant of the alcohol dehydrogenase 1B (ADH1B) gene, which is associated with lower prevalence of alcohol abuse and dependence. Other measures included age, education, marital status, smoking and physical activity, body mass index, diabetes, hypertension, and cardiovascular diseases.ResultsAt study entry, rs1229984 G→A polymorphism was associated with lower prevalence of regular use of alcohol and decreased consumption among regular users. Six years later, 502 men (14.2%) showed evidence of cognitive impairment. Abstainers and irregular drinkers had higher odds of cognitive impairment than regular drinkers (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.00-1.51, after adjustment for other measured factors). The rs1229984 G→A polymorphism did not decrease the odds of cognitive impairment (AA/GG OR = 1.35, 95% CI = 0.29-6.27; GA/GG OR = 1.05, 95% CI = 0.71-1.55).ConclusionsAlcohol consumption, including heavy regular drinking and abuse, is not a direct cause of cognitive impairment in later life. Our results are consistent with the possibility, but do not prove, that regular moderate drinking decreases the risk of cognitive impairment in older men.
| S-EPMC3962996 | biostudies-literature
Project description:Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (G×E) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygenic scores (PS) were included. Overall study quality was moderate, with lower ratings for the polygenic methods in the haplotype and candidate-gene score studies. Heterogeneity in investigated environmental exposures, genetic factors, and outcomes was substantial. Most studies (N?=?30) reported at least one significant G×E interaction, but overall evidence was weak. The majority (N?=?26) found results in line with differential susceptibility and diathesis-stress frameworks. Future studies should pay more attention to methodological and statistical rigor, and focus on replication efforts. Additional work is needed before firm conclusions can be drawn about the importance of G×E in the etiology of substance use.
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Project description:OBJECTIVE:This study aimed to examine among veterans (a) whether alcohol consumption patterns are associated with probability of psychiatric symptoms and (b) whether an alcohol use disorder (AUD) history explains psychiatric symptoms among nondrinkers. METHOD:Data were collected from 3,003 veterans (20.5% women). Gender-stratified logistic models examined the association between alcohol consumption pattern and the odds of symptoms of posttraumatic stress disorder (PTSD), depression, and suicidality. Two types of models were tested: four-group models comparing moderate drinkers to nondrinkers, light, and heavy drinkers; and five-group models separating nondrinkers by AUD history. RESULTS:In four-group models for both genders, compared with moderate drinkers, hazardous drinkers were more likely to have psychiatric symptoms. Among men, nondrinkers were more likely to have symptoms of depression and suicidality but not PTSD. Among women, nondrinkers and light drinkers were more likely to have PTSD symptoms. In the five-group model for men, odds of symptoms were higher for nondrinkers with an AUD history and hazardous drinkers. Compared to nondrinkers without an AUD history and light drinkers, male nondrinkers with an AUD history had higher odds of psychiatric symptoms. In the five-group model for women, the odds of symptoms were higher for hazardous drinkers. Female nondrinkers with an AUD history had higher odds of a positive depression screen. Odds of a positive PTSD screen were higher for female nondrinkers (with and without an AUD history) and light drinkers. CONCLUSIONS:For male veterans, there was a protective effect of moderate drinking (compared with abstinence) that disappeared when nondrinkers without an AUD history were separated. However, results for women showed a protective effect of moderate drinking with regard to PTSD that persisted even when an AUD history was taken into account.
| S-EPMC6082130 | biostudies-literature
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.
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