Association between alcohol consumption and Alzheimer’s disease: A Mendelian randomization Study

Abstract

Observational studies have suggested that a U-shaped relationship exists between alcohol consumption and Alzheimer's disease, with light-moderate drinkers at lower risk of developing Alzheimer's disease. A two-sample Mendelian randomization approach was used to examine whether alcohol consumption causally effects the risk of developing Alzheimer's disease. We used summary level genome-wide association data for alcohol consumption from the UK biobank, alcohol dependence from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety, and Alzheimer's disease from the International Genomics of Alzheimer's Project. Variants associated with alcohol consumption were combined using an inverse variance weighted fixed-effects approach. We found no evidence of a causal association between genetically predicted alcohol consumption These findings contrast with those of recent systematic reviews of observational studies.

Association Between Alcohol Use Disorders and Dementia in 262,703 Dementia-free Finnish Adults: Is Cardiovascular Disease a Mediator?

“…Contradicting to the previous MR study (13), our g-formula results supported a causal association between AUD and dementia. This inconsistency may relate to the different definitions of AUDwe used the formal medical diagnosis from the hospital records, whereas in the MR study AUD was assessed using the Alcohol Use Disorder Identification Test.…”

“…On the contrary, a meta-analysis of 15 prospective cohort studies with 2-8 years of follow-up (10) and an overview of 3 systematic reviews (11) both reported no association between heavy drinking and dementia. A recent Mendelian randomization (MR) study, which is not influenced by confounding and overcomes the main bias in observational epidemiology by design (12), also showed no causal association between AUD and dementia (13). This MR study nevertheless may suffer from the violation of the exclusion restriction assumption that threats the validity of the results (14,15).…”

Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States

“…39 A two-sample Mendelian randomization study found no evidence of a causal relationship between alcohol consumption and late-onset Alzheimer's disease; they did, however, find evidence of an association between alcohol consumption and earlier Alzheimer's age of onset. 14 A polygenic risk score based two-sample Mendelian randomization analysis of many putative modifiable Alzheimer's disease risk factors and Alzheimer's disease phenotypes found no association between alcohol consumption and Alzheimer's disease. 15 Generally consistent with these findings, our Mendelian randomization analyses were also predominantly null.…”

“…10 Prior Mendelian randomization investigations have largely found null associations between alcohol use and cognitive impairment or dementia. [11][12][13][14][15] Several of those studies only assessed cognitive impairment and relied on individual single nucleotide polymorphisms (SNPs) in the alcohol metabolism genes ALDH2 and ADH1B as genetic instruments. [11][12][13] Only one such study of 235 rural Chinese individuals found an increased risk of cognitive impairment with increased alcohol consumption.…”

“…12 All studies were conducted in predominately Asian or European ancestries populations. [11][12][13][14][15] Further research in additional populations and genetic loci leveraging Mendelian randomization approaches may clarify the relationship between alcohol consumption and dementia risk.…”