The overall goals of the proposed MESA Family Study are to locate and identify genes contributing to subclinical cardiovascular disease (CVD), assessed by coronary calcium (CAC) and carotid intimal medial wall thickness (IMT), and to evaluate the impact of lifestyle and environment on the manifestations of these genetic susceptibilities to CVD in U.S. minority populations. These goals will be addressed in a study of 2700 individuals from 900 sibships (sibtrios), evenly distributed among African-Americans, Hispanic-Americans, and Chinese-Americans, utilizing the existing framework of the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA).
In Aim 1, this MESA Family Study will determine the extent of genetic contribution to variation in coronary calcium (EBCT and helical-gated CT scan) and carotid artery intimal-medial thickness (IMT) (B-mode ultrasound) in non-majority U.S. populations. This will be accomplished by phenotyping 1800 siblings of 900 MESA index cases, In Aim 2, using the MESA Study resources (Data Coordination Center, Central Laboratory, CT and Ultrasound Reading Center, 6 Clinical Field Centers), and bringing to bear the combined resources and cardiovascular genetic epidemiology expertise at Cedars-Sinai Medical Center and Wake-Forest School of Medicine, candidate regions in the human genome linked to these quantitative subclinical cardiovascular disease traits (coronary calcium and IMT) will be identified by genome scan approaches. This will be followed by initiation of positional cloning and candidate gene identification within these regions.
In Aim 3, we will further pursue gene localization and identification by testing positional and biological candidate genes in both family based and case control association studies. Whereas the purpose of MESA is to assess subclinical CVD and identify 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 subclinical CVD risk factors. In combination with traditional risk factor assessment, such inherited markers should be useful in the management of patients with vascular disease, through targeted diagnostic testing and pharmacologic intervention, and in the identification of subjects who could benefit from specific prevention protocols, thus resulting in an increase in the overall well-being of the US population.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Olson, Jean
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Wake Forest University Health Sciences
Public Health & Prev Medicine
Schools of Medicine
United States
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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
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; 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
Kraja, Aldi T; Cook, James P; Warren, Helen R et al. (2017) New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475?000 Individuals. Circ Cardiovasc Genet 10:
van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P et al. (2017) Discovery of novel heart rate-associated loci using the Exome Chip. Hum Mol Genet 26:2346-2363
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

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