Dataset Information

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

ABSTRACT:

Background & aim

The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD.

Methods

The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results.

Results

Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (β = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias.

Conclusions

This genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.

SUBMITTER: Wang M

PROVIDER: S-EPMC10547005 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

Wang Mengmeng M Cornelis Marilyn C MC Zhang Zhizhong Z Liu Dandan D Lian Xuegan X

Clinical nutrition (Edinburgh, Scotland) 20211001 11

<h4>Background & aim</h4>The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD.<h4>Methods</h4>The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancest ...[more]

PMID: 34656958

Similar Datasets

Project description:BackgroundClozapine is an effective antipsychotic medication for patients with treatment-resistant schizophrenia. Previous studies revealed that smoking, alcohol intake, and coffee consumption altered the metabolism of clozapine. However, causal associations between substance use and clozapine levels were not sufficiently established.MethodsSeveral genome-wide association studies provided genetic tools for six measures of substance use, including age of smoking, cigarettes per day, smoking cessation, smoking initiation, coffee consumption, and alcohol consumption (GWASs). Utilizing the CLOZUK consortium's dataset, their associations with clozapine and its metabolite concentrations were evaluated. All GWAS data were collected from the European population. Mendelian randomization (MR) estimations from each genetic test were combined using inverse variance weighted (IVW) meta-analysis in combination with complementing techniques (such as weighted median and MR Egger). We also analyze horizontal pleiotropy and heterogeneity using various sensitivity analyses.ResultsGenetically predicted higher level of smoking initiation was significantly associated with reduced clozapine (β = -0.14, P = 4.53E-04) concentrations and norclozapine concentrations (β = -0.14, P = 3.33E-04), and increased coffee consumption was significantly associated with lower level of clozapine concentrations (β = -0.42, P = 1.70E-14), norclozapine concentrations (β = -0.27, P = 1.51E-07), and the metabolic ratio of clozapine to norclozapine (β = -0.15, P = 5.35E-07), survived after the Bonferroni correction (P = 0.05/6 = 0.008). In sensitivity analyses, the weighted median and MR Egger methods demonstrated directionally consistent effects. In addition, our sensitive test indicated no significant horizontal pleiotropy and heterogeneity (P > 0.05). However, other measures of substance use (age of initiation smoking, cigarettes per day, smoking cessation, and drinks per week) were not associated with clozapine metabolism.ConclusionOur investigation revealed a correlation between greater smoking initiation and coffee consumption and reduced blood levels of clozapine and norclozapine. Providing clinicians with guidance on how to adjust clozapine levels for clozapine-treated patients.

Project description:BackgroundThe association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.Materials and methodsIn this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p < 5 × 10-8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.ResultsThe genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512-1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p < 5 × 10-8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676-1.125, p = 0.292).ConclusionOur MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.

Dataset Information

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

Background & aim

Methods

Results

Conclusions

Publications

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets