TY - JOUR
T1 - Genetic investigation into the differential risk of atrial fibrillation among black and white individuals
AU - Roberts, Jason D.
AU - Hu, Donglei
AU - Heckbert, Susan R.
AU - Alonso, Alvaro
AU - Dewland, Thomas A.
AU - Vittinghoff, Eric
AU - Liu, Yongmei
AU - Psaty, Bruce M.
AU - Olgin, Jeffrey E.
AU - Magnani, Jared W.
AU - Huntsman, Scott
AU - Burchard, Esteban G.
AU - Arking, Dan E.
AU - Bibbins-Domingo, Kirsten
AU - Harris, Tamara B.
AU - Perez, Marco V.
AU - Ziv, Elad
AU - Marcus, Gregory M.
N1 - Publisher Copyright:
© 2016 American Medical Association.
PY - 2016/7
Y1 - 2016/7
N2 - 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 effectmethod 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 ameta-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.
AB - 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 effectmethod 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 ameta-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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U2 - 10.1001/jamacardio.2016.1185
DO - 10.1001/jamacardio.2016.1185
M3 - Article
C2 - 27438321
AN - SCOPUS:85015802775
SN - 2380-6583
VL - 1
SP - 442
EP - 450
JO - JAMA Cardiology
JF - JAMA Cardiology
IS - 4
ER -