NHLBI Deep Whole Genome Sequencing
Overview[edit]
The NIH National Heart, Lung and Blood Institute (NHLBI) has committed to deep (30x coverage) whole genome sequencing for all of the collected samples from 9 (now 11) of its ongoing disease-specific research projects (detailed below). The total will approach 20,000 individuals. The sequencing will start in February, 2015 and is projected to be finished by the end of December.
The sequencing is divided by project among four sequencing centers: Broad Institute, University of Washington, New York Genome Center and Illumina (commercial). Groups at University of Washington and University of Michigan will share the tasks of data handling and project coordination. UW is designated as the Data Coordinating Center (DCC) and will coordinate phenotype information and the monthly conference calls. U.Mich is designated as the Informatics Research Core (IRC) with responsibility for creating a unified variant call set. The sequence and genotype data will be deposited to dbGaP, initially in a special protected "Exchange Area" accessible only to project participants. it is expected that each contributing disease-specific study will write their own paper on findings from whole genome sequencing.
Within the U.Mich component of the project, we provide:
- Track data production
- Generate a primary call set including SNPs, short indels and structural variants
- BRAVO variant browser
- ENCORE analysis server
- Conduct population genetic analyses
- TOPMed phenotype working groups
- NIH Data Commons
September 2016 Site Visit[edit]
Table of year 2 studies[edit]
Table of year 1 studies[edit]
PI Name(s) | Institution | Disease / Phenotype | Study Title | Sample Size | Seq Center | Populations |
---|---|---|---|---|---|---|
Kathleen C. Barnes | Johns Hopkins University | asthma genetics in high prevalence populations of African descent | New approaches for empowering studies of asthma in populations of African descent | 1,100 | Illumina | African descent Barbados families with > 40% of asthmatic members |
John Blangero (contact); Joanne E. Curran; David C. Glahn | UT Health Sciences Center San Antonio | cardiometabolic risk factors | Whole genome sequencing to identify causal genetic variants influencing CVD risk | 1,142 | Illumina | Mexican American in SAFHS extended pedigrees |
Esteban Gonzalez Burchard | University of California, San Francisco | racial and ethnic disparities in response to asthma treatment | Pharmacogenomics of bronchodilator response in minority children with asthma | 1,500 | NYGC | 500 AA, 500 Puerto Rican and 500 Mexican of extremely non-responding asthma patients |
Patrick Thomas Ellinor (contact); Emelia J. Benjamin; Kathryn L. Lunetta | Massachusetts General Hospital | early atrial fibrillation | Identification of common genetic variants for atrial fibrillation and PR interval | 2,799 | Broad | Atrial fibrillation cases all European American (uses Framingham as controls) |
Braxton D. Mitchell | University of Maryland School of Medicine | cardiometabolic risk factors | Identification and functional characterization of a gene influencing LDL cholesterol on 5q | 1,100 | Broad | Old Order Amish large extended pedigrees |
Vasan Ramachandran (contact) | Boston University | longitudinal cardiometabolic risk factors | Framingham Heart Study | 4,089 | Broad | 3 generation European American pedigrees |
Edwin K. Silverman | Brigham and Women's Hospital | genetic risk and protective variants for COPD in African American and European American populations | Genetic epidemiology of COPD | 2,000 | UW | 1,000 EA and 900 AA of extremely severe, early onset COPD patients vs extreme healthy smokers |
Scott T. Weiss | Brigham and Women's Hospital | asthma genetics in high prevalence Hispanic population | The genetic epidemiology of asthma in Costa Rica | 1,198 | UW | Costa Rica is a special Hispanic population with asthma prevalence at 24% |
Adolfo Correa James Wilson (contact) |
University of Mississippi | cardiometabolic risk factors | Jackson Heart Study | 3,499 | UW | AA mixed family and population based |
Stephen T. McGarvey | International Health Institute, Brown University | genes influencing obesity | Samoan Family Study of Overweight and Diabetes | 384 | UW | with planned imputation to other pedigree members |
Susan Redline | Brigham and Women's Hospital | genes influencing sleep apnea | Cleveland Family Study | 1,000 | UW | 500 African American, 500 European American |
(This information from Cathy Laurie as of Dec 2, 2014, with numbers subsequently updated. Two more studies added February 15, 2015.)
U.Mich personnel[edit]
Goncalo tentatively designated different people to contribute to the four major commitments:
- Data Monitoring web site: Hyun Min Kang, Kevin Li
- Variant Calling Pipeline: Hyun Min Kang, Mary Kate Wing, Chris Scheller, additional students
- Population Genetic Analyses: Sebastian Zoellner, Keng-Han Lin
- Cross Study Analyses: Shawn Lee, Xiang Zhou
- Liaison with study investigators: Tom Blackwell, Ellen Schmidt