Genetic Ancestry Is Associated With Subclinical Cardiovascular Disease in African-Americans and Hispanics From the Multi-Ethnic Study of Atherosclerosis

Department of Family and Prevention Medicine, University of California, San Diego, CA 92093-0965, USA.
Circulation Cardiovascular Genetics (Impact Factor: 4.6). 12/2009; 2(6):629-36. DOI: 10.1161/CIRCGENETICS.109.876243
Source: PubMed


Differences in cardiovascular disease (CVD) burden exist among racial/ethnic groups in the United States, with African-Americans having the highest prevalence. Subclinical CVD measures have also been shown to differ by race or ethnicity. In the United States, there has been a significant intermixing among racial/ethnic groups creating admixed populations. Very little research exists on the relationship of genetic ancestry and subclinical CVD measures.
These associations were investigated in 712 black and 705 Hispanic participants from the Multi-Ethnic Study of Atherosclerosis candidate gene substudy. Individual ancestry was estimated from 199 genetic markers using STRUCTURE. Associations of ancestry and coronary artery calcium (CAC) and common and internal carotid intima media thickness were evaluated using log-binomial and linear regression models. Splines indicated linear associations of ancestry with subclinical CVD measures in African-Americans but presence of threshold effects in Hispanics. Among African-Americans, each SD increase in European ancestry was associated with an 8% (95% CI, 1.02 to 1.15; P=0.01) higher CAC prevalence. Each SD increase in European ancestry was also associated with a 2% (95% CI -3.4% to -0.5%, P=0.008) lower common carotid intima media thickness in African-Americans. Among Hispanics, the highest tertile of European ancestry was associated with a 34% higher CAC prevalence (P=0.02) when compared with the lowest tertile.
The linear association of ancestry and subclinical CVD suggests that genetic effects may be important in determining CAC and carotid intima media thickness among African-Americans. Our results also suggest that CAC and common carotid intima media thickness may be important phenotypes for further study with admixture mapping.

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Available from: Shweta Choudhry, Sep 04, 2014
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    • "It is also possible that different biological pathways or different genetic variants within the same pathways are at play resulting in genetic heterogeneity between European and African ancestral populations in the mechanisms leading to atherogenesis and CAC. This is borne out by the observation that greater CAC burden is associated with higher levels of European admixture in AA populations [43], suggesting that genetic variants specific to EA play a more important role in the development of CAC than those of African origin. Indeed, there are several lines of evidence suggesting distinct pathophysiology of CAC in AAs, including lower CAC scores despite greater risk factor burden and higher rates of CHD in AA samples [7,9,10,23,24,26,44-46]. "
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    ABSTRACT: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants. We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis. Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region. While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.
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    • "Prior studies have shown that despite similar cardiac risk factors, Hispanic subgroups have varying degrees of subclinical CVD, including higher coronary artery calcium (CAC) scores and inflammation as measured by C-reactive protein [12,22-24]. This may be attributed to the genetic diversity in Hispanic subgroups [25]. The low prevalence of hypertension among Mexicans, despite acculturation, might be explained by the geographic proximity to their native land, which may play a stronger role in preservation of family ties and traditions despite length of residency in the U.S. and English language acquisition [26]. "
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