Investigation of Causal Effect of Atrial Fibrillation on Alzheimer Disease: A Mendelian Randomization Study
Yuesong Pan1,2, Yilong Wang1,2, Yongjun Wang1,2
1Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing China.
Insights
This study investigated if atrial fibrillation (AF) causally increases Alzheimer disease risk. Using Mendelian randomization, no evidence supported a causal link between AF and Alzheimer disease, suggesting the observed association may not be causal.
Area of Science:
- Neuroscience
- Genetics
- Cardiology
Background:
- Observational studies link atrial fibrillation (AF) to increased dementia and Alzheimer disease (AD) risk.
- The causal nature of this association remains uncertain.
Purpose of the Study:
- To investigate the potential causal association between atrial fibrillation and Alzheimer disease using a robust genetic approach.
Main Methods:
- Employed a 2-sample Mendelian randomization (MR) approach.
- Utilized large genome-wide association study data for AF (N=1,030,836) and AD (N=455,258).
- Analyzed single nucleotide polymorphisms (SNPs) associated with AF as instrumental variables for AD risk.
Main Results:
- MR analysis with 93 SNPs showed no significant association between genetically predicted AF and Alzheimer disease risk (OR=1.002, P=0.47).
- Mendelian randomization-Egger regression indicated no significant genetic pleiotropy (P=0.70).
Conclusions:
- This study provides no genetic evidence to support a causal relationship between atrial fibrillation and the risk of developing Alzheimer disease.
Abstract:
Background Atrial fibrillation (AF) has been shown to be associated with an increased risk of dementia as well as Alzheimer disease in observational studies. Whether this association reflects causal association is still unclear. The purpose of this study was to examine the causal association of AF with Alzheimer disease. Methods and Results We used a 2-sample Mendelian randomization approach to evaluate the causal effect of AF on Alzheimer disease. Summary data on the association of single nucleotide polymorphisms with AF were obtained from a recently published genome-wide association study with up to 1 030 836 individuals and data on single nucleotide polymorphism-Alzheimer disease association from another genome-wide association study with up to 455 258 individuals. AF was mainly diagnosed according to International Classification of Diseases, Ninth Revision (ICD-9 or ICD-10) and Alzheimer disease was mainly diagnosed according to clinical criteria (eg, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA] criteria). Effect estimates were calculated using the inverse-variance weighted method. The Mendelian randomization analysis showed nonsignificant association of genetically predicted AF with risk of Alzheimer disease (odds ratio=1.002, 95% CI: 0.996-1.009, P=0.47) using 93 single nucleotide polymorphisms as the instruments. Mendelian randomization-Egger indicated no evidence of genetic pleiotropy (intercept=0.0002, 95% CI: -0.001 to 0.001, P=0.70). Conclusions This Mendelian randomization analysis found no evidence to support causal association between AF and Alzheimer disease.
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