This is a first resubmission of the MESA Family Study, HL071205. The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to sub-clinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT) in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios or larger), evenly distributed among African-Americans and Hispanic Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA).
In Aim 1, the MESA Family Study will determine the extent of genetic contribution to variation in CAC (EBCT and helical-gated CT scan) and IMT (B-mode ultrasound) in these two populations.
This aim will be accomplished by examination (phenotyping) of 1800 siblings from 900 MESA index cases (evenly divided between African-Americans and Hispanic-Americans).
In Aim 2, biological candidate regions in the human genome linked to these quantitative sub-clinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches, including fine mapping of the best regions.
This aim will use the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers) and the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine.
In Aim 3, gene localization and identification will be accomplished by association studies of positional as well as biological candidate genes in the subjects from the 3 minority populations of MESA (African-Americans, Hispanic-Americans, and Chinese-Americans). Whereas the purpose of MESA (the parent study) is to assess sub-clinical CVD and identify epidemiological risk factors in multi-ethnic populations, the purpose of the MESA Family Study is to identify the genes (quantitative trait loci, or QTLs) that contribute to these sub-clinical CVD risk factors. In combination with traditional risk factor assessment, identified inherited markers should be useful in the management of patients with vascular disease. These results will permit targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols, thus result in an increase in the overall well being of the US population.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071051-02
Application #
6784702
Study Section
Special Emphasis Panel (ZRG1-SNEM-5 (03))
Program Officer
Olson, Jean
Project Start
2003-08-01
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$330,445
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Prokopenko, Dmitry; Sakornsakolpat, Phuwanat; Fier, Heide Loehlein et al. (2018) Whole-Genome Sequencing in Severe Chronic Obstructive Pulmonary Disease. Am J Respir Cell Mol Biol 59:614-622
Robinson-Cohen, Cassianne; Bartz, Traci M; Lai, Dongbing et al. (2018) Genetic Variants Associated with Circulating Fibroblast Growth Factor 23. J Am Soc Nephrol 29:2583-2592
Balakrishnan, Poojitha; Jones, Miranda R; Vaidya, Dhananjay et al. (2018) Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA). Int J Environ Res Public Health 15:
McKeown, Nicola M; Dashti, Hassan S; Ma, Jiantao et al. (2018) Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis. Diabetologia 61:317-330
Fernández-Rhodes, Lindsay; Malinowski, Jennifer R; Wang, Yujie et al. (2018) The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis. PLoS One 13:e0200486
Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E et al. (2017) Genetic Variants Associated with Circulating Parathyroid Hormone. J Am Soc Nephrol 28:1553-1565
Yoneyama, S; Yao, J; Guo, X et al. (2017) Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. Int J Obes (Lond) 41:324-331
Manichaikul, Ani; Wang, Xin-Qun; Sun, Li et al. (2017) Genome-wide association study of subclinical interstitial lung disease in MESA. Respir Res 18:97
Manichaikul, Ani; Sun, Li; Borczuk, Alain C et al. (2017) Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc 14:628-635
Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A et al. (2016) Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels. Nat Commun 7:10494

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