Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 10, Issue 2, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.116.001569
Keywords
adult; admixture mapping; atherosclerosis; cardiovascular disease; carotid intima-media thickness; European ancestry; prevalence
Funding
- National Heart, Lung, and Blood Institute (NHLBI)
- NHLBI [N02-HL-64278, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
- National Human Genome Research Institute [U01HG004402]
- [HHSN268201500003I]
- [N01-HC-95159]
- [N01-HC-95160]
- [N01-HC-95161]
- [N01-HC-95162]
- [N01-HC-95163]
- [N01-HC-95164]
- [N01-HC-95165]
- [N01-HC-95166]
- [N01-HC-95167]
- [N01-HC-95168]
- [N01-HC-95169]
- [UL1-TR-001079]
- [UL1-TR-000040]
- [DK063491]
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Background-Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease among admixed African Americans compared with other populations, suggesting a rationale for admixture mapping. Methods and Results-We estimated local European ancestry (LEA) using Local Ancestry inference in adMixed Populations using Linkage Disequilibrium method (LAMP-LD) and evaluated the association with common carotid artery intima-media thickness (cCIMT) using multivariable linear regression analysis among 1554 African Americans from MESA (Multi-Ethnic Study of Atherosclerosis). We conducted secondary analysis to examine the significant cCIMT-LEA associations with clinical cardiovascular disease events. We observed genome-wide significance in relation to cCIMT association with the SERGEF gene (secretion-regulating guanine nucleotide exchange factor; beta=0.0137; P=2.98x10(-4)), also associated with higher odds of stroke (odds ratio=1.71; P=0.02). Several regions, in particular CADPS gene (Ca2+-dependent secretion activator 1) region identified in MESA, were also replicated in the ARIC cohort (Atherosclerosis Risk in Communities). We observed other cCIMT-LEA regions associated with other clinical events, most notably the regions harboring CKMT2 gene (creatine kinase, mitochondrial 2) and RASGRF2 gene (Ras protein-specific guanine nucleotide-releasing factor 2) with all clinical events except stroke, the LRRC3B gene (leucine-rich repeat containing 3B) with myocardial infarction, the PRMT3 gene (protein arginine methyltransferase 3) with stroke, and the LHFPL2 gene (lipoma high mobility group protein I-C fusion partner-like 2) with hard and all coronary heart disease. Conclusions-We identified several novel LEA regions, in addition to previously identified genetic variations, associated with cCIMT and cardiovascular disease events among African Americans.
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