Population Architecture using Genomics and Epidemiology (PAGE)

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 ]]>
The Atherosclerosis Risk in Communities (ARIC) Study is a longitudinal study to examine cardiovascular health risks in subjects (n=15729, age range 45-64), baseline was taken in 1987-1989. Genotyping was performed at the University of Texas Health Science Center using the ABI TaqMan platform.The Coronary Artery Risk Development in Young Adults (CARDIA) study was founded in 1986 to study the development of cardiovascular disease in young adults (n=5115, age range 18-30 at baseline). Genotyping was performed at the University of Texas Health Science Center using the ABI TaqMan platform.The Cardiovascular Health Study (CHS) was founded in 1988, with additional baseline samples taken in 1992, is an observational study of risk factors for cardiovascular disease in adults 65 years or older (n=5888, age range 65-100). Genotyping was performed at the University of Texas Health Science Center using the ABI TaqMan platform.Epidemiologic Architecture for Genes Linked to Environment (EAGLE) uses data gathered by the CDC for National Health and Nutrition Examination Surveys (NHANES; n=14,998, age range 12-95), a cross-sectional study of the US population collected in 1984-1994 (NHANES III), and 1999-2002 (NHANES 99-02). Subjects are from three ancestries: European American, African American, and Hispanic. Genotyping was performed at Vanderbilt University using the Sequenom, ABI ABI TaqMan, Illumina BeadXpress and Open Array platforms.The Multiethnic Cohort is a nested case control study of subjects (n=74,303, age range 45-78) collected from 1993-1996, with a goal of evaluation of dietary and other environmental contributions to the racial-ethnic variability in cancer risk. Subjects are primarily of five ancestries, European American, African American, Hispanic, Native Hawaiian, and Japanese. Genotyping was performed at the Cancer Research Center of Hawaii using the AB OpenArray platform and at the University of Southern California using the ABI TaqMan platform.The Strong Heart Study was established to investigate the prevalence, severity of, and risk factors for cardiovascular disease among American Indians. The Strong Heart Study consists of 1) a cohort population of 4,500 American Indian men and women recruited from centers in three geographic regions: Arizona, Oklahoma and North and South Dakota with 3 clinic visits and ongoing Mortality and Morbidity surveillance (Phase I: 1989-1991; Phase II: 1993-1995; Phase III: 1998-1999, respectively), and 2) a multigenerational family genetic study examined in Phase IV (2001-2003) and Phase V (2005-2008) recruited from the same centers and including 3,838 individuals from 94 families, of whom 825 are Phase III participants re-examined in Phase IV. The data for this analysis were from (2) above from the Arizona recruitment site.The Women's Health Initiative (WHI) is a case-cohort founded to address the most common causes of death, disability and impaired quality of life in postmenopausal women. Subjects (n=141,645, age range 50-79) were collected over a 15 year period starting in 1991. Subjects are from primarily five ancestries, European American, African American, Hispanic, Native American, and Asian. Genotyping was performed at Translational Genomics Research Institute using the Illumina BeadXpress platform.Meta-analysis of results from the contributing individual studies: ARIC, CARDIA, CHS, EAGLE, MEC, SHS, SHFS & WHI.PMID:28426890)
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