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 journalArticle

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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Carotid Intima-Media Thickness
Common Carotid Artery
African Americans
Atherosclerosis
Cohort Studies
Cardiovascular Diseases
Genes
Stroke
Guanine Nucleotide-Releasing Factor 2
Protein-Arginine N-Methyltransferases
Mitochondrial Form Creatine Kinase
High Mobility Group Proteins
Guanine Nucleotide Exchange Factors
ras Proteins
Lipoma
Linkage Disequilibrium
Protein C
Leucine
Population
Coronary Disease

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

Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies. / Shendre, Aditi; Wiener, Howard; Irvin, Marguerite R.; Zhi, Degui; Limdi, Nita A.; Overton, Edgar T.; Wassel, Christina L.; Divers, Jasmin; Rotter, Jerome I.; Post, Wendy S; Shrestha, Sadeep.

In: Circulation: Cardiovascular Genetics, Vol. 10, No. 2, e001569, 01.04.2017.

Research output: Contribution to journalArticle

Shendre, A, Wiener, H, Irvin, MR, Zhi, D, Limdi, NA, Overton, ET, Wassel, CL, Divers, J, Rotter, JI, Post, WS & Shrestha, S 2017, 'Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies', Circulation: Cardiovascular Genetics, vol. 10, no. 2, e001569. https://doi.org/10.1161/CIRCGENETICS.116.001569
Shendre, Aditi ; Wiener, Howard ; Irvin, Marguerite R. ; Zhi, Degui ; Limdi, Nita A. ; Overton, Edgar T. ; Wassel, Christina L. ; Divers, Jasmin ; Rotter, Jerome I. ; Post, Wendy S ; Shrestha, Sadeep. / Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events among African Americans in 2 Large Cohort Studies. In: Circulation: Cardiovascular Genetics. 2017 ; Vol. 10, No. 2.
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AU - Limdi, Nita A.

AU - Overton, Edgar T.

AU - Wassel, Christina L.

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N2 - 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.

AB - 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.

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