The Institute for Personalized Medicine (IPM) BioMe Biobank is a consented, EMR-linked medical care setting biorepository of the Mount Sinai Medical Center (MSMC) drawing from a population of over 70,000 inpatients and 800,000 outpatient visits annually. MSMC serves diverse local communities of upper Manhattan, including Central Harlem (86% African American), East Harlem (88% Hispanic Latino), and Upper East Side (88% Caucasian/white) with broad health disparities. IPM BioMe Biobank populations include 28% African American, 38% Hispanic Latino predominantly of Caribbean origin, 23% Caucasian/White. IPM BioMe Biobank disease burden is reflective of health disparities with broad public health impact. Biobank operations are fully integrated in clinical care processes, including direct recruitment from clinical sites waiting areas and phlebotomy stations by dedicated Biobank recruiters independent of clinical care providers, prior to or following a clinician standard of care visit. Recruitment currently occurs at a broad spectrum of over 30 clinical care sites.
This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (<a href="http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bihttps://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1">phs000356</a>).

Stanford contributed samples to the PAGE study that can act as a population reference dataset across the globe. Therefore this dataset includes reference individuals, without phenotypes, chosen to help infer ancestry that will help us understand the diverse samples available in PAGE. The complete dataset comprises individuals of European, African, Asian, Oceanian, and Native American descent, from a total of over 50 populations. A subset of these individuals from Puno, Peru and Easter Island (Rapa Nui), Chile, are included in the PAGE samples that were whole genome sequenced in 2015. Additional details are available in the Study Acknowledgments.
The Global Reference Panel comprises 6 sample sets: - A population sample of Andean individuals primarily of Quechuan/Aymaran ancestry from Puno, Peru - A population sample of Easter Island (Rapa Nui), Chile - Individuals of indigenous origin from Oaxaca, Mexico - Individuals of indigenous origin from Honduras - Individuals of indigenous origin from Colombia - Individuals of indigenous origin from the Nama and Khomani KhoeSan populations of the Northern Cape, South Africa
In addition, we genotyped publicly available samples that will be hosted on the Bustamante lab website (<a href="https://bustamantelab.stanford.edu/">https://bustamantelab.stanford.edu/</a>). These comprise large public datasets to provide an open reference dataset for the world:
<ul>
<li>The additional related individuals from the Americas in the Human Genome Diversity Panel (H952) plus all additional samples from the Americas - A subset of the unrelated individuals from the Maasai in Kinyawa, Kenya (MKK) dataset from the International Hapmap Project hosted at Coriell</li>
</ul>
Additional samples will be available for restricted use with a data access agreement with the Bustamante Lab.
This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (<a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356">phs000356</a>).

The Multiethnic Cohort (MEC) has established a large biorepository of blood and urine (N=67,000) and cryopreserved lymphocytes (N=15,000) linked to extensive, prospectively collected risk factors (e.g., diet, smoking, physical activity), biomarkers and clinical data for five racial/ethnic groups. This cohort study of over 215,000 men and women in Hawaii and California is unique in that it is population-based and includes large representations of older adults (45-75 yrs at baseline) for five US racial/ethnic groups (Japanese Americans, African Americans, European Americans, Latinos and Native Hawaiians) at varying risks of chronic diseases. Within the PAGE investigation, the MEC proposes to study: 1) diseases for which we have DNA available for large numbers of cases and controls (breast, prostate, and colorectal cancer, diabetes, and obesity); 2) important cancers that are less common (e.g., lung, pancreas, endometrial cancers, NHL) but for which we propose to pool our data with other funded groups; 3) common traits that are risk factors for these diseases (e.g., body mass index/weight, waist-to-hip ratio, height) and 4) relevant disease-associated biomarkers (e.g., fasting insulin and lipids, steroid hormones). The specific aims are: 1) To determine the population-based epidemiologic profile (allele frequency, main effect, heterogeneity by disease characteristics) of putative causal variants in the five racial/ethnic groups in the MEC; 2) for variants displaying effect heterogeneity across ethnic/racial groups, we will utilize differences in LD to identify a more complete spectrum of associated variants at these loci; 3) investigate gene x gene and gene x environment interactions to identify modifiers; 4) examine the associations of putative causal variants with already measured intermediate phenotypes (e.g., plasma insulin, lipids, steroid hormones); and 5) for variants that do not fall within known genes, start to investigate their relationships with gene expression and epigenetic patterns in small genomic studies.
This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356">phs000356</a>.

This substudy phs000227 PAGE WHI contains genotypes generated using BeadXpress and Metabochip, produced as part of NHGRI's PAGE project. Summary level phenotypes for the WHI Cohort study participants can be viewed at the top-level study page <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000200">phs000200</a> WHI Cohort. Individual level phenotype data and molecular data for all WHI top-level study and substudies are available by requesting Authorized Access to the WHI Cohort study <a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000200">phs000200</a>.
WHI 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. These chronic diseases are the major causes of death, disability and frailty in older women of all races and socioeconomic backgrounds.
This cohort is sponsored by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), involves 161,808 women aged 50-79, and is one of the most definitive, far-reaching clinical trials of post-menopausal women's health ever undertaken in the U.S. Women were recruited between 1993 to 1998 at 40 centers across the US and follow up is planned to continue until at least 2015. The WHI Clinical Trial and Observational Study focused on many of the inequities in women's health research and will continue to provide practical information to women and their physicians about hormone therapy, dietary patterns, calcium/vitamin D supplementation, and their effects on the prevention of heart disease, cancer and osteoporotic fractures.
The WHI has two major parts: a randomized Clinical Trial and an Observational Study. The randomized controlled Clinical Trial (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: - Hormone Therapy Trials (HT): This 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 took hormone pills or a placebo (inactive pill) until the Estrogen plus Progestin and Estrogen Alone trials were stopped early in July 2002 and March 2004, respectively. All HT participants continued to be followed without intervention until close-out. - 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 followed either their usual eating pattern or a low-fat dietary pattern. - Calcium/Vitamin D Trial (CaD): This 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 took calcium and vitamin D pills or a placebo.
The Observational Study (OS) is examining the relationship between lifestyle, health and risk factors and specific disease outcomes. This component involves tracking the medical history and health habits of 93,676 women.
To fully examine the profile of gene and environment interaction, or "epidemiologic architecture," we will comprehensively evaluate such putative genuine variants in the Women's Health Initiative This large study population not only enables us to examine the population incidence for racial and ethnic subgroups and associated risks of rigorously defined, incident diseases (specific aim 1) but allows us to investigate associated risks given in-depth information on various environmental exposures and disease risk factors as well as three randomized interventions (hormone therapy; low-fat dietary modification; calcium + vitamin D supplements) (specific aim 2). The prospective and longitudinal collection of biospecimens, intermediate outcomes, and phenotypic characteristics, such as bone mineral density, hormone concentrations, breast density, or inflammation will further permit us to link genetic variants to relevant intermediate phenotypes, which will potentially provide important clues to the biological basis of the genuine associations (specific aim 3). For a variety of outcomes we will genotype within this 4-year project 72,000 participants for disease-specific putative genuine variants. Information generated from this study will be critical to determine the health impact of any given undisputable variant. Findings may also provide valuable insights into disease pathways and mechanisms, and targets for disease screening, prevention, and treatment.
This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (<a href="https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356">phs000356</a>).

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