Insight on the Genetics of Atrial Fibrillation in Puerto Rican Hispanics

Abstract

Non-Hispanic whites present with higher atrial fibrillation (AF) prevalence than other racial minorities living in the mainland USA. In two hospital-based studies, Puerto Rican Hispanics had a lower prevalence of atrial fibrillation of 2.5% than non-Hispanic Whites with 5.7%. This data is particularly controversial because Hispanics possess a higher prevalence of traditional risk factors for developing AF yet have a lower AF prevalence. This phenomenon is known as the atrial fibrillation paradox. Despite recent advancements in understanding AF, its pathogenesis remains unclear. In this study, we compared a genetic dataset of Puerto Rican Hispanics to 111 SNP known to be associated with AF in a large European cohort and determine if they are associated with AF susceptibility in our cohort. To achieve this aim, we performed a secondary analysis of existing data using the following two studies: (1) The Pharmacogenetics of Warfarin in Puerto Ricans study and the (2) A Genomic Approach for Clopidogrel in Caribbean Hispanics, and assess for the presence of European SNPs associated with AF from the genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation. We used data from 555 cardiovascular Puerto Rican Hispanic patients, consisting of 486 control and 69 cases. We found that the following SNPs showed significant association with AF in PHR: rs2834618, rs6462079, rs7508, rs2040862, and rs10458660. Some of these SNPs are proteins involved in lysosomal activities responsible for breaking ceramides to sphingosines and collagen deposition around atrial cardiomyocytes. Furthermore, we performed a machine learning analysis and determined that Native American admixture and heart failure were strongly predictive of AF in PHR. For the first time, this study provides some genetic insight into AF’s mechanisms in a Puerto Rican Hispanic cohort.

Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies

“…Details of the excluded studies and the reasons for exclusion are provided in Supplementary Table S2 . 37 studies were selected from the main search for data extraction 8 , 9 , 10 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 and an additional 7 were found from references of meta-analyses or registries. 59 , 60 , 61 , 62 , 63 , 64 , 65 Study characteristics for the discovery analyses and supporting studies are provided in Supplementary Tables S3 and S4 .…”