期刊
BMC MEDICAL GENETICS
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2350-14-75
关键词
Atherosclerosis; Coronary artery calcium; Genetics; Meta-analysis; African-American
资金
- NIH from NHLBI [R01-HL-087700, R01-HL-088215]
- NIH from NIDDK [R01-DK-8925601, R01-DK-075681]
- National Heart, Lung, and Blood Institute
- University of Alabama at Birmingham [N01-HC-48047, N01-HC-95095]
- University of Minnesota [N01-HC-48048, N01-HC-95163]
- Northwestern University [N01-HC-48049, N01-HC-95164]
- Kaiser Foundation Research Institute [N01-HC-48050]
- Tufts-New England Medical Center [N01-HC-45204]
- Wake Forest University [N01-HC-45205, N01-HC-95165]
- Harbor-UCLA Research and Education Institute [N01-HC-05187, N01-HC-95169]
- University of California, Irvine [N01-HC-45134, N01-HC-95100]
- Jackson Heart Study (JHS): Jackson State University [N01-HC-95170]
- University of Mississippi [N01-HC-95171]
- Tougaloo College [N01-HC-95172]
- Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington [N01-HC-95159]
- Regents of the University of California [N01-HC-95160]
- Columbia University [N01-HC-95161]
- Johns Hopkins University [N01-HC-95162, N01-HC-95168]
- University of Vermont [N01-HC-95166]
- New England Medical Center [N01-HC-95167]
- Cedars-Sinai Medical Center [R01-HL-071205]
- University of Virginia [R01-HL-071205]
- National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-95095, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45204, N01-HC-45205, N01-HC-05187, N01-HC-45134]
- NHLBI's Candidate-gene Association REsource (CARe) Study
- National Heart, Lung, and Blood Institute (NHLBI)
- United States Environmental Protection Agency (EPA)
- NHLBI [N02-HL-6-4278]
- National Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED [R01 HL087698-01]
- NIH/National Institute of Nursing Research [NR008153-01]
- NIH/National Center for Research Resources [M01-RR000052]
- National Institutes of Health from National Heart, Lung, Blood Institute [HL085571, HL087660, HL100245]
- AXA Research Fund
- [R01-HL084099]
- [U01-HG004729]
- [R01HL071051]
- [R01HL071205]
- [R01HL071250]
- [R01HL071251]
- [R01HL071252]
- [R01HL071258]
- [R01HL071259]
- [RD83169701]
- [HL58625-01A1]
- [HL59684]
- [HL071025-01A1]
- [R01-DK071224]
- [R01-DK-090505]
- [U01-HL108636]
- [K24-HL107643]
- [R01-HL113147]
Background: 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. Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with similar to 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. Results: Heritability of CAC was lower in AA (similar to 30%) than previously reported for EA (similar to 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. Conclusions: 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据