Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies

Aditi Shendre, Howard Wiener, Marguerite R. Irvin, Degui Zhi, Nita A. Limdi, Edgar T. Overton, Christina L. Wassel, Jasmin Divers, Jerome I. Rotter, Wendy S Post, Sadeep Shrestha

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Abstract

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; β=0.0137; P=2.98×10 - 4), also associated with higher odds of stroke (odds ratio=1.71; P=0.02). Several regions, in particular CADPS gene (Ca 2+ -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.

Original languageEnglish (US)
Article numbere001569
JournalCirculation: Cardiovascular Genetics
Volume10
Issue number2
DOIs
StatePublished - Apr 1 2017

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Keywords

  • admixture mapping
  • adult
  • atherosclerosis
  • cardiovascular disease
  • carotid intima-media thickness
  • European ancestry
  • prevalence

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Shendre, A., Wiener, H., Irvin, M. R., Zhi, D., Limdi, N. A., Overton, E. T., Wassel, C. L., Divers, J., Rotter, J. I., Post, W. S., & Shrestha, S. (2017). Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies. Circulation: Cardiovascular Genetics, 10(2), [e001569]. https://doi.org/10.1161/CIRCGENETICS.116.001569