Dataset Information

Population Architecture using Genomics and Epidemiology (PAGE)

ABSTRACT:

PAGE II (2013-2017) seeks to expand understanding gained during PAGE I and similar studies of how ancestry-specific differences in allele frequencies and LD may explain differences in risks of common traits and conditions. Recent studies have identified rare genetic variants that are likely to contribute to common diseases and traits and observed that rare variants likely to be functional, such as those in coding and regulatory regions, tend to be population-specific. PAGE II has genotyped over 50,000 samples using MEGA, an Illumina high density custom exomechip array. The MEGA data is being imputed in PAGE to the 1000 Genomes panel. PAGE also sequenced 1,000 samples representative of 21 populations from the Americas. PAGE has harmonized phenotype data for ~300 trait variables. These datasets will be analyzed to continue emphasis on characterizing population-level disease risks in non-European-descent individuals. Cohorts in PAGE II are: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, HCHS/SOL, Strong Heart Studies), ISMMS (Mount Sinai BioMe Biobank), MEC (Multiethnic Cohort), WHI (Women's Health Initiative), and Stanford University (PAGE Global Reference Panel). Genotyping services were provided by the Center for Inherited Disease Research (CIDR) and sequence data were provided by the McDonnell Genome Institute at Washington University School of Medicine.

PAGE I (2008-2013): The first phase of PAGE examined putative causal genetic variants across approximately 100,000 African Americans, Asian Americans, American Indians, European Americans, Hispanic Americans, and Native Hawaiians from four groups representing nine large U.S.-based cohorts. Two genotyping approaches were employed - targeted genotyping of selected SNPs identified in genome-wide association studies of common disease, and a large-scale effort focused on the Metabochip array, which facilitated trans-ethnic fine mapping of several diseases of public health importance. Cohorts in PAGE I were: CALiCo (Causal Variants Across the Life Course, a consortium of ARIC, CARDIA, CHS, HCHS/SOL, Strong Heart Cohort Study, Strong Heart Family Study), EAGLE (Epidemiologic Architecture for Genes Linked to Environment, based on 3 National Health and Nutrition Examination Surveys (NHANES)), MEC (Multiethnic Cohort) and WHI (Women's Health Initiative).

Logistical and scientific support is provided by the PAGE Coordinating Center and the NHGRI Division of Genomic Medicine. PAGE II is funded by the NHGRI and the NIMHD.

To access PAGE studies currently available in dbGaP, please click on the links below.Please note that some PAGE studies belong to larger cohorts and have been included as PAGE substudies. For those studies, there is an additional link to the parent study.

phs000223 PAGE-ARIC and phs000280 ARIC Cohort
phs000236 PAGE-CARDIA and phs000285 CARDIA Cohort
phs000301 PAGE-CHS and phs000287 CHS Cohort
phs000559 PAGE-EAGLE-BioVu
phs000208 PAGE-EAGLE-NHANES
phs000555 PAGE-HCHS/SOL and phs000810 HCHS/SOL Cohort
phs000220 PAGE-MEC
phs000580 PAGE-SHS and SHFS
phs001033 PAGE Global Reference Panel
phs000227 PAGE-WHI and phs000200 WHI Cohort

PROVIDER: phs000356 | dbGaP |

SECONDARY ACCESSION(S): PRJNA168052PRJNA168051

REPOSITORIES: dbGaP

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	README.txt	Txt
	phs000356.PAGE_Analysis.analysis-PI.MULTI.tar.gz	Other
	phs000356.PAGE_Analysis_v2.analysis-PI.MULTI.tar.gz	Other
	phs000356.pha003580.txt.gz	Txt
	phs000356.pha003581.txt.gz	Txt

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Project description:The Women's Health Initiative (WHI) is a long-term national health study that has focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women. The original WHI study included 161,808 postmenopausal women enrolled between 1993 and 1998. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI has two major parts: a partial factorial randomized Clinical Trial (CT) and an Observational Study (OS); both were conducted at 40 Clinical Centers nationwide. The CT enrolled 68,132 postmenopausal women between the ages of 50-79 into trials testing three prevention strategies. If eligible, women could choose to enroll in one, two, or all three of the trial components. The components are: <ul> <li>Hormone Therapy Trials (HT): This double-blind component examined the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component with an intact uterus were randomized to estrogen plus progestin (conjugated equine estrogens [CEE], 0.625 mg/d plus medroxyprogesterone acetate [MPA] 2.5 mg/d] or a matching placebo. Women with prior hysterectomy were randomized to CEE or placebo. Both trials were stopped early, in July 2002 and March 2004, respectively, based on adverse effects. All HT participants continued to be followed without intervention until close-out.</li> <li>Dietary Modification Trial (DM): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and coronary heart disease. Study participants were randomized to either their usual eating pattern or a low-fat dietary pattern.</li> <li>Calcium/Vitamin D Trial (CaD): This double-blind component began 1 to 2 years after a woman joined one or both of the other clinical trial components. It evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component were randomized to calcium (1000 mg/d) and vitamin D (400 IU/d) supplements or a matching placebo.</li> </ul> The Observational Study (OS) examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the CT. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years. The original protocol allowed for follow-up until March 2005, after which participants were invited to enroll in the first WHI Extension Study for follow-up through 2010. Participants were invited again to participate in the second WHI Extension Study with continued follow up from 2010 to 2015. As of March 31, 2011 there were 93,122 women enrolled in the second extension. As part of the second Extension, 80+ year old women were asked to consent to an In Person Visit at their homes during which additional blood samples were collected and various measurements were taken (such as blood pressure, height, weight, waist circumference, grip strength, etc). The WHI Cohort is utilized in the following dbGaP substudies. 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 phs000200 WHI Cohort. <ul> <li><a href="./study.cgi?study_id=phs000386">phs000386</a> WHI SHARe</li> <li><a href="./study.cgi?study_id=phs000281">phs000281</a> GO-ESP WHISP</li> <li><a href="./study.cgi?study_id=phs000315">phs000315</a> WHI GARNET</li> <li><a href="./study.cgi?study_id=phs000503">phs000503</a> WHISE</li> </ul>

Project description:The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were examined with the baseline visit occurring in 1987-89, the second visit in 1990-92, the third visit in 1993-95, the fourth visit in 1996-98, and the fifth visit in 2011-13. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. In the Community Surveillance Component, these four communities were investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducted community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005. Community Surveillance for non-cohorts ended in event year 2014. ARIC is currently funded through October 31, 2021. The ARIC Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page <a href="study.cgi?study_id=phs000280">phs000280</a> ARIC Cohort. <ul> <li><a href="study.cgi?study_id=phs000557">phs000557</a> ARIC_CARe</li> <li><a href="study.cgi?study_id=phs000090">phs000090</a> GENEVA_ARIC</li> <li><a href="study.cgi?study_id=phs000223">phs000223</a> PAGE_CALiCo_ARIC</li> <li><a href="study.cgi?study_id=phs000398">phs000398</a> GO-ESP: HeartGo_ARIC</li> <li><a href="study.cgi?study_id=phs000668">phs000668</a> CHARGE_ARIC</li> <li><a href="study.cgi?study_id=phs000860">phs000860</a> MICORTEX</li> </ul>

Project description:Objectives The Cardiovascular Health Study (CHS) is a study of risk factors for development and progression of CHD and stroke in people aged 65 years and older. The objectives of the Cardiovascular Health Study are to: 1) quantify associations of conventional and hypothesized risk factors with CHD and stroke; 2) assess the associations of non-invasive measures of subclinical disease with the incidence of CHD and stroke; 3) quantify the associations of risk factors with subclinical disease; 4) characterize the natural history of CHD and stroke, and identify factors associated with clinical course; and 5) describe the prevalence and distributions of risk factors, non-invasive measures of subclinical disease, and clinical CHD and stroke. Background The study originated in 1988 from the recommendations of an NHLBI workshop on the management of CHD in the elderly. This is the most extensive study undertaken by the NHLBI to study CVD exclusively in an elderly population. Initially funded for six years, it was renewed for a second six year period in 1994 and recently was renewed with limited support for the Coordinating Center, the Laboratory and the Steering Committee. Grant funding from several sources has supported an additional clinic visit in 2005-2006 and continued morbidity and mortality follow-up. Subjects The 5,888 study participants were recruited from four U.S. communities and have undergone extensive clinic examinations for evaluation of markers of subclinical cardiovascular disease. The original cohort totaled 5,201 participants. A new cohort was recruited in 1992. The 687 participants in the new cohort are predominately African-American and were recruited at three of the four field centers. Design The 2,962 women and 2,239 men were examined yearly from 1989 through 1999. The added minority cohort of 256 men and 431 women was examined from 1992 to 1999. Examination components have included medical history questionnaires, measurement of ankle-brachial index, abdominal and carotid ultrasound studies, echocardiograms, ambulatory electrocardiograms, cerebral magnetic resonance imaging, spirometry and retinal photographs over the past decade. The most extensive evaluations were at study entry (baseline) and again in 1992-1993 to assess change in subclinical disease measures. CHS has undertaken extensive follow-up for ascertainment of cardiovascular events including incident claudication, myocardial infarction, congestive heart failure, stroke and death. Genetic Research The Cardiovascular Health Study has expanded its research mission into the study of genetic factors underlying CVD and other disorders using DNA that was collected from blood samples from most participants. Subsets of CHS participants have been genotyped in large-scale genotyping projects, including thousands of SNP genotypes for candidate gene regions as part of the NHLBI Candidate gene Association Resource (CARe) and genome-wide genotyping as part of the NHLBI SNP Typing for Association with Multiple Phenotypes from Existing Epidemiologic Data (STAMPEED). Whole exome sequencing of an overlapping subset of CHS participants was performed through the NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP). The Cardiovascular Health Study Cohort is utilized in the following dbGaP substudies. 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 phs000287 Cardiovascular Health Study Cohort. <li><a href="./study.cgi?study_id=phs000226">phs000226</a> STAMPEED: Cardiovascular Health Study (CHS)</li> <li><a href="./study.cgi?study_id=phs000301">phs000301</a> PAGE: CaLiCo: Cardiovascular Health Study</li> <li><a href="./study.cgi?study_id=phs000377">phs000377</a> CARe Cardiovascular Health Study</li> <li><a href="./study.cgi?study_id=phs000400">phs000400</a> GO-ESP-CHS: Cardiovascular Health Study Component of the Exome Sequencing Project</li> <li><a href="./study.cgi?study_id=phs000667">phs000667</a> CHARGE-S: Cardiovascular Health Study (CHS)</li>

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Population Architecture using Genomics and Epidemiology (PAGE)

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