Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States
Forthcoming
This Github repository contains the data management and analytic scripts to produce the following manuscript:
Background: In observational studies, the association between alcohol consumption and dementia is mixed. Methods: We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer’s disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal. Results: Alcohol consumption was not associated with late-onset Alzheimer’s disease using two-sample MR (OR=1.15, 95% confidence interval (CI):[0.78, 1.72]). In HRS, doubling weekly alcohol consumption was not associated with dementia (African ancestries, n=1,322, OR=1.00, 95% CI [0.45, 2.25]; European ancestries, n=7,160, OR=1.37, 95% CI [0.53, 3.51]) or cognitively impaired, non-dementia (African ancestries, n=1,322, OR=1.17, 95% CI [0.69, 1.98]; European ancestries, n=7,160, OR=0.75, 95% CI [0.47, 1.22]). Conclusion: Alcohol consumption was not associated with cognitively impaired, non-dementia or dementia status.
We thank the participants and staff of the Health and Retirement Study. This research was supported by the National Institutes of Heath: National Institute on Aging (R01 AG055406, R01 AG067592).
Publicly available datasets were analyzed in this study. This data can be found here: Health and Retirement Study health and covariate data are available here: https://hrs.isr.umich.edu/data-products. Health and Retirement Study genetic data are available here: dbGaP Study Accession: phs000428.v2.p2 (https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000428.v2.p2).
inclusion_exclusion.Rmd: performing inclusion/exclusion operations on cohort data
alc_dem_sample_descriptions.Rmd: descriptive statistics and tables
alcohol_GSCAN_2019_LOAD_Kunkle_2019_two_sample_mr.Rmd: contains the two-sample Mendelian randomization analysis
gscan_dpw_1smr_xs_data_prep.Rmd: data prep for one-sample Mendelian randomization analysis
gscan_dpw_1smr_xs_assumptions.Rmd: testing the Mendelian randomization assumptions
gscan_dpw_1smr_xs_model.Rmd: contains the actual one-sample Mendelian randomization analysis and conventional logistic regression analysis
fit_models.R: contains custom functions for model fitting
fit_relevance_models.R: contains custom functions for some Mendelian randomization assumptions testing
gscan_dpw_1smr_xs_model_functions.R: contains custom functions for one-sample Mendelian randomization analysis
formatting_functions.r: contains custom functions for data formatting and labelling