Dataset Information

Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

ABSTRACT: BACKGROUND AND AIMS:Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. METHODS:The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66). RESULTS:In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. CONCLUSION:Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.

SUBMITTER: Vargas JD

PROVIDER: S-EPMC4738145 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Vargas Jose D JD Manichaikul Ani A Wang Xin-Qun XQ Rich Stephen S SS Rotter Jerome I JI Post Wendy S WS Polak Joseph F JF Budoff Matthew J MJ Bluemke David A DA

Atherosclerosis 20151208

<h4>Background and aims</h4>Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds.<h4>Methods</h4>The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from pu ...[more]

PMID: 26789557

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Project description:RationaleObstructive sleep apnea (OSA) has been postulated to contribute to idiopathic pulmonary fibrosis by promoting alveolar epithelial injury via tractional forces and intermittent hypoxia.ObjectivesTo determine whether OSA is associated with subclinical interstitial lung disease (ILD) and with biomarkers of alveolar epithelial injury and remodeling.MethodsWe performed cross-sectional analyses of 1,690 community-dwelling adults who underwent 15-channel in-home polysomnography and thoracic computed tomographic imaging in the Multi-Ethnic Study of Atherosclerosis. We measured the obstructive apnea-hypopnea index (oAHI) by polysomnography and high-attenuation areas (HAAs) and interstitial lung abnormalities (ILAs) by computed tomography. Serum matrix metalloproteinase-7 (MMP-7) and surfactant protein-A (SP-A) were measured by ELISA in 99 participants. We used generalized linear models to adjust for potential confounders.ResultsThe mean age was 68 years, and the mean forced vital capacity was 97% predicted. The median oAHI was 8.4 events/h, and 32% had an oAHI greater than 15. After adjusting for demographics, smoking, and center, an oAHI greater than 15 was associated with a 4.0% HAA increment (95% confidence interval [CI], 1.4-6.8%; P = 0.003) and 35% increased odds of ILA (95% CI, 13-61%; P = 0.001). However, there was evidence that these associations varied by body mass index (BMI) (P for interaction = 0.08 and 0.04, respectively). Among those with a BMI less than 25 kg/m2, an oAHI greater than 15 was associated with a 6.1% HAA increment (95% CI, 0.5-12%; P = 0.03) and 2.3-fold increased odds of ILA (95% CI, 1.3-4.1; P = 0.005). Among those with a BMI greater than 30 kg/m2, an oAHI greater than 15 was associated with 1.8-fold greater odds of ILA (95% CI, 1.1-2.9; P = 0.01) but was not associated with HAA. There were no meaningful associations detected among those with a BMI of 25-30 kg/m2. Greater oAHI was associated higher serum SP-A and MMP-7 levels, particularly among those with a BMI less than 25 kg/m2.ConclusionsModerate to severe OSA is associated with subclinical ILD and with evidence of alveolar epithelial injury and extracellular matrix remodeling in community-dwelling adults, an association that is strongest among normal-weight individuals. These findings support the hypothesis that OSA might contribute to early ILD.

Dataset Information

Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

Publications

Common genetic variants and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

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