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. 2016 Jul 1;1(4):442-50.
doi: 10.1001/jamacardio.2016.1185.

Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals

Jason D Roberts  1 , Donglei Hu  2 , Susan R Heckbert  3 , Alvaro Alonso  4 , Thomas A Dewland  1 , Eric Vittinghoff  5 , Yongmei Liu  6 , Bruce M Psaty  7 , Jeffrey E Olgin  1 , Jared W Magnani  8 , Scott Huntsman  2 , Esteban G Burchard  9 , Dan E Arking  10 , Kirsten Bibbins-Domingo  11 , Tamara B Harris  12 , Marco V Perez  13 , Elad Ziv  2 , Gregory M Marcus  1
Affiliations

Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals

Jason D Roberts et al. JAMA Cardiol. .

Abstract

Importance: White persons have a higher risk of atrial fibrillation (AF) compared with black individuals despite a lower prevalence of risk factors. This difference may be due, at least in part, to genetic factors.

Objectives: To determine whether 9 single-nucleotide polymorphisms (SNPs) associated with AF account for this paradoxical differential racial risk for AF and to use admixture mapping to search genome-wide for loci that may account for this phenomenon.

Design, setting, and participants: Genome-wide admixture analysis and candidate SNP study involving 3 population-based cohort studies that were initiated between 1987 and 1997, including the Cardiovascular Health Study (CHS) (n = 4173), the Atherosclerosis Risk in Communities (ARIC) (n = 12 341) study, and the Health, Aging, and Body Composition (Health ABC) (n = 1015) study. In all 3 studies, race was self-identified. Cox proportional hazards regression models and the proportion of treatment effect method were used to determine the impact of 9 AF-risk SNPs among participants from CHS and the ARIC study. The present study began July 1, 2012, and was completed in 2015.

Main outcomes and measures: Incident AF systematically ascertained using clinic visit electrocardiograms, hospital discharge diagnosis codes, death certificates, and Medicare claims data.

Results: A single SNP, rs10824026 (chromosome 10: position 73661450), was found to significantly mediate the higher risk for AF in white participants compared with black participants in CHS (11.4%; 95% CI, 2.9%-29.9%) and ARIC (31.7%; 95% CI, 16.0%-53.0%). Admixture mapping was performed in a meta-analysis of black participants within CHS (n = 811), ARIC (n = 3112), and Health ABC (n = 1015). No loci that reached the prespecified statistical threshold for genome-wide significance were identified.

Conclusions and relevance: The rs10824026 SNP on chromosome 10q22 mediates a modest proportion of the increased risk of AF among white individuals compared with black individuals, potentially through an effect on gene expression levels of MYOZ1. No additional genetic variants accounting for a significant portion of the differential racial risk of AF were identified with genome-wide admixture mapping, suggesting that additional genetic or environmental influences beyond single SNPs in isolation may account for the paradoxical racial risk of AF among white individuals and black individuals.

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Figures

Figure 1
Figure 1
Manhattan Plots of Admixture Mapping for Incident Atrial Fibrillation Among Blacks from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D).
Figure 1
Figure 1
Manhattan Plots of Admixture Mapping for Incident Atrial Fibrillation Among Blacks from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D).
Figure 1
Figure 1
Manhattan Plots of Admixture Mapping for Incident Atrial Fibrillation Among Blacks from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D).
Figure 1
Figure 1
Manhattan Plots of Admixture Mapping for Incident Atrial Fibrillation Among Blacks from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D).
Figure 2
Figure 2
Manhattan Plots of Admixture Mapping Restricted to Incident Cases of Atrial Fibrillation Among Blacks that Developed the Arrhythmia in the Absence of Baseline Pre-Specified Risk Factors* from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D). *Hypertension, Diabetes, Heart failure, and History of Myocardial Infarction
Figure 2
Figure 2
Manhattan Plots of Admixture Mapping Restricted to Incident Cases of Atrial Fibrillation Among Blacks that Developed the Arrhythmia in the Absence of Baseline Pre-Specified Risk Factors* from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D). *Hypertension, Diabetes, Heart failure, and History of Myocardial Infarction
Figure 2
Figure 2
Manhattan Plots of Admixture Mapping Restricted to Incident Cases of Atrial Fibrillation Among Blacks that Developed the Arrhythmia in the Absence of Baseline Pre-Specified Risk Factors* from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D). *Hypertension, Diabetes, Heart failure, and History of Myocardial Infarction
Figure 2
Figure 2
Manhattan Plots of Admixture Mapping Restricted to Incident Cases of Atrial Fibrillation Among Blacks that Developed the Arrhythmia in the Absence of Baseline Pre-Specified Risk Factors* from CHS (A), ARIC (B), Health ABC (C), and meta-analysis (D). *Hypertension, Diabetes, Heart failure, and History of Myocardial Infarction
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