Investigation of Causal Effect of Atrial Fibrillation on Alzheimer Disease: A Mendelian Randomization Study

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.