Genomewide linkage and peakwide association analyses of carotid plaque in caribbean hispanics

Chuanhui Dong, Ashley Beecham, Susan Slifer, Liyong Wang, Susan H Blanton, Clinton B Wright, Tatjana Rundek, Ralph L Sacco

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background and Purpose- Atherosclerosis is a complex subclinical cardiovascular disorder with a substantial genetic component. This study sought to identify genetic loci influencing carotid plaque in 2 independent samples. Methods- B-mode ultrasound was performed to determine the presence and area of carotid plaque. Variance components analysis was used to test for linkage using 383 autosomal microsatellite markers in 1308 subjects from 100 Dominican families. Multiple linear and logistic regression models were used to investigate the association between plaque traits and 18 904 single nucleotide polymorphisms under the 1-logarithm of odds unit down regions of linkage peaks in an independent community-based data set (N=941, 41% Dominicans) from the Northern Manhattan Study. Results- After adjustment for age, hypertension, diabetes mellitus, cigarette pack-years, body mass index, and waist-to-hip ratio, significant heritability was detected for plaque presence (h 2=0.50±0.14, P<0.0001) and plaque area (h 2=0.17±0.04, P<0.0001). Quantitative and dichotomous trait linkage analyses obtained similar results and identified 4 regions with multipoint logarithm of odds scores ≥2.00 on 7q36, 11p15, 14q32, and 15q23. In the association analysis of the 4 linkage peaks, several single nucleotide polymorphisms in or near SOX6, FSD2, AP3S2, EFTUD1, and MYOD1 were associated with carotid plaque traits with a nominal P≤0.0005 in the Northern Manhattan Study data set and with a P≤0.01 in Northern Manhattan Study Dominican subset. Conclusions- Carotid plaque has considerable heritability and may be influenced by loci on chromosomes 11p15, 14q32, and 15q23. The SOX6 gene within the bone morphogenic protein pathway could be a candidate for carotid plaque. Larger independent studies are needed to validate these findings.

Original languageEnglish
Pages (from-to)2750-2756
Number of pages7
JournalStroke
Volume41
Issue number12
DOIs
StatePublished - Dec 1 2010

Fingerprint

Hispanic Americans
Single Nucleotide Polymorphism
Logistic Models
Genetic Loci
Waist-Hip Ratio
Tobacco Products
Microsatellite Repeats
Linear Models
Atherosclerosis
Diabetes Mellitus
Analysis of Variance
Body Mass Index
Chromosomes
Hypertension
Bone and Bones
Genes
Proteins
Datasets

Keywords

  • association
  • Caribbean Hispanics
  • carotid plaque
  • heritability
  • linkage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Genomewide linkage and peakwide association analyses of carotid plaque in caribbean hispanics. / Dong, Chuanhui; Beecham, Ashley; Slifer, Susan; Wang, Liyong; Blanton, Susan H; Wright, Clinton B; Rundek, Tatjana; Sacco, Ralph L.

In: Stroke, Vol. 41, No. 12, 01.12.2010, p. 2750-2756.

Research output: Contribution to journalArticle

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AU - Wright, Clinton B

AU - Rundek, Tatjana

AU - Sacco, Ralph L

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