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

Research output: Contribution to journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies'. Together they form a unique fingerprint.

Cite this