Rare-variant association tests in longitudinal studies, with an application to the Multi-Ethnic Study of Atherosclerosis (MESA).
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ABSTRACT:
SUBMITTER: He Z
PROVIDER: S-EPMC5696115 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Rare-variant association tests in longitudinal studies, with an application to the Multi-Ethnic Study of Atherosclerosis (MESA).
He Zihuai Z Lee Seunggeun S Zhang Min M Smith Jennifer A JA Guo Xiuqing X Palmas Walter W Kardia Sharon L R SLR Ionita-Laza Iuliana I Mukherjee Bhramar B
Genetic epidemiology 20171027 8
Over the past few years, an increasing number of studies have identified rare variants that contribute to trait heritability. Due to the extreme rarity of some individual variants, gene-based association tests have been proposed to aggregate the genetic variants within a gene, pathway, or specific genomic region as opposed to a one-at-a-time single variant analysis. In addition, in longitudinal studies, statistical power to detect disease susceptibility rare variants can be improved through join ...[more]
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Project description:To investigate the cross-sectional relationship between objectively measured sleep characteristics and multiple indices of adiposity in racially/ethnically diverse older adults within the MESA Sleep study (n = 2,146).7-day actigraphy was used to assess sleep duration, sleep efficiency, and night-to-night variability. Body mass index (BMI), waist circumference, and total body fat were modeled continuously and according to obesity cut-points. Models were adjusted for demographic, socioeconomic, and behavioral variables.Participants who slept less than 6 hours a night had significantly higher BMI, waist circumference, and body fat relative to those who slept 7-8 hours. Those who slept less than 5 hours had a 16% higher prevalence of general obesity (BMI ? 30 vs. < 25 kg/m(2)) (95% [CI]: 0.08-0.24) and a 9% higher prevalence of abdominal obesity (waist circumference: women ? 88 centimeters, men ? 102 centimeters; 95% CI: 0.03-0.16) compared to those who slept 7-8 hours. Results were similar for sleep efficiency and night-to-night sleep variability.Among an older multi-ethnic cohort, we found robust associations across multiple indices of sleep and adiposity. Targeting sleep characteristics may be of benefit in obesity interventions, but more research is needed to rule out reverse causality.
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Project description:NHLBI TOPMed: Multi-ethnic Study of Atherosclerosis (MESA)
| PRJNA396087 | ENA
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Project description:<p><b>MESA</b><br/> The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.</p> <p>Participants were recruited from six field centers across the United States: Wake Forest University, Columbia University, Johns Hopkins University, University of Minnesota, Northwestern University and University of California - Los Angeles. Each participant received an extensive physical exam to determine coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, carotid intimal-medial wall thickness and presence of echogenic lucencies in the carotid artery, lower extremity vascular insufficiency, arterial wave forms, electrocardiographic (ECG) measures, standard coronary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors. Selected repetition of subclinical disease measures and risk factors at follow-up visits allows study of the progression of disease. Blood samples have been assayed for putative biochemical risk factors and stored for case-control studies. DNA has been extracted and lymphocytes cryopreserved (for possible immortalization) for study of candidate genes and possibly, genome-wide scanning, expression, and other genetic techniques. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality.</p> <p>In addition to the six Field Centers, MESA involves a Coordinating Center, a Central Laboratory, and Central Reading Centers for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Ultrasound, and Electrocardiography (ECG). Protocol development, staff training, and pilot testing were performed in the first 18 months of the study. The first examination took place over two years, from July 2000 - July 2002. It was followed by four examination periods that were 17-20 months in length. Participants have been contacted every 9 to 12 months throughout the study to assess clinical morbidity and mortality.</p> <p><b>MESA Family</b><br/> The general goal of the MESA Family Study, an ancillary study to MESA funded by a grant from NHLBI, is to apply modern genetic analysis and genotyping methodologies to delineate the genetic determinants of early atherosclerosis. This is being accomplished by utilizing all the current organizational structures of the <b>Multi-Ethnic Study of Atherosclerosis (MESA)</b> and Genetic Centers at Cedars-Sinai Medical Center and University of Virginia.</p> <p>In the MESA Family Study, the goal is to locate and identify genes contributing to the genetic risk for cardiovascular disease (CVD), by looking at the early changes of atherosclerosis within families (mainly siblings). 2128 individuals from 594 families, yielding 3,026 sibpairs divided between African Americans and Hispanic-Americans, were recruited by utilizing the existing framework of MESA. MESA Family studied siblings of index subjects from the MESA study and from new sibpair families (with the same demographic characteristics) and is determining the extent of genetic contribution to the variation in coronary calcium (obtained via CT Scan) and carotid artery wall thickness (B-mode ultrasound) in the two largest non-majority U.S. populations. In a small proportion of subjects, parents of MESA index subjects participating in MESA Family were studied but only to have blood drawn for genotyping.</p> <p>The MESA Family cohort was recruited from the six MESA Field Centers. MESA Family participants underwent the same examination as MESA participants during May 2004 - May 2007. DNA was extracted and lymphocytes immortalized for study of candidate genes, genome-wide linkage scanning, and analyzed for linkage with these subclinical cardiovascular traits. While linkage analysis is the primary approach being used, an additional aspect of the MESA Family Study takes advantage of the existing MESA study population for testing a variety of candidate genes for association with the same subclinical traits. Genotyping and data analysis will occur throughout the study.</p> <p><b>MESA Air</b><br/> The general goal of the Multi-Ethnic Study of Atherosclerosis and Air Pollution ('MESA Air') is to prospectively examine the relation between an individual level assessment of long-term ambient air pollution exposures (including PM<sub>2.5</sub> and the progression of subclinical cardiovascular disease in a multi-city, multi-ethnic cohort. MESA Air will also prospectively examine the relationship between an individual level assessment of long-term ambient air pollution exposures and the incidence of cardiovascular disease, including myocardial infarction and cardiovascular death. MESA AIR is funded by a grant from the United States Environmental Protection Agency to the University of Washington and subcontracts from the UW to other participating institutions.</p> <p>MESA Air will assess if ambient air pollution is associated with changes over time in subclinical measures of atherosclerosis and plasma markers of inflammation, oxidative damage, and endothelial activation in a longitudinal data model, adjusting for age, race/ethnicity, socioeconomic status, and specific cardiovascular risk factors (such as diabetes, hypertension, smoking, and diet). The study will similarly assess if the incidence of cardiovascular events is associated with long-term exposure to ambient air pollution, using a proportional hazards model. The study includes refinement of statistical tools, and explores joint/independent effects of acute and long-term pollutant exposure in the occurrence of cardiovascular disease.</p> <p>The MESA Air study is built on the foundation of the ongoing MESA study. The parent MESA Study cohort is located in six geographic areas ('Field Centers') that capture tremendous exposure heterogeneity, comparable to or greater than the variability in locations of prior U.S. cohort studies. In addition to the six Field Centers, the study involves a Coordinating Center, a Central Laboratory, and Reading Centers for Computed Tomography (CT), ultrasound and air pollution data.</p> <p>The cohort for the MESA Air study currently includes 6226 subjects: 5479 enrolled in the parent MESA study; 257 recruited specifically for this study, and 490 recruited from the MESA Family study. The entire MESA Air cohort will be followed over a 10-year project period for the occurrence of cardiovascular disease events.</p> <p>On two occasions over the ten-year study period, 3600 subjects from the MESA Air cohort, residing in nine locales, will undergo computed tomography scanning to assess presence and extent of coronary artery calcification (CAC), and ultrasound of the carotid artery to determine intima-media thickness (IMT). We will also repeatedly assess plasma markers of inflammation, oxidative damage, and endothelial function in 720 subjects.</p> <p>MESA Air adds state-of-the-art air pollution exposure assessment information to the MESA cohort study, and introduces new subjects and outcome measures to achieve our aims. The study will assess long-term individual-level exposure to ambient air pollutants for each subject using community-scale monitoring, outdoor spatial variation, subject proximity to pollution sources, pollutants' infiltration efficiency, and personal time-activity information. The exposure models will be validated using detailed monitoring in a subset of subjects.</p> <p><b>The MESA Cohort is utilized in the following dbGaP substudies.</b> To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs000209 MESA Cohort. <ul> <li><a href="./study.cgi?study_id=phs000420">phs000420</a> MESA SHARe</li> <li><a href="./study.cgi?study_id=phs000283">phs000283</a> MESA CARe</li> </ul> </p>
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Project description:Differences in residential location as well as race/ethnicity and dietary habits may result in differences in inorganic arsenic (iAs) exposure. We investigated the association of exposure to iAs with race/ethnicity, geography, and dietary intake in a random sample of 310 White, Black, Hispanic, and Chinese adults in the Multi-Ethnic Study of Atherosclerosis from 6 US cities with inorganic and methylated arsenic (ΣAs) measured in urine. Dietary intake was assessed by food-frequency questionnaire. Chinese and Hispanic race/ethnicity was associated with 82% (95% CI: 46%, 126%) and 37% (95% CI: 10%, 70%) higher urine arsenic concentrations, respectively, compared to White participants. No differences were observed for Black participants compared to Whites. Urine arsenic concentrations were higher for participants in Los Angeles, Chicago, and New York compared to other sites. Participants that ate rice ≥2 times/week had 31% higher urine arsenic compared to those that rarely/never consumed rice. Participants that drank wine ≥2 times/week had 23% higher urine arsenic compared to rare/never wine drinkers. Intake of poultry or non-rice grains was not associated with urinary arsenic concentrations. At the low-moderate levels typical of the US population, exposure to iAs differed by race/ethnicity, geographic location, and frequency of rice and wine intake.
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