Building on our 25-year track record in comprehensive genomic studies and addressing NHGRI's goal for this RFA, we propose to create, apply and test a powerful, reliable and general strategy for comprehensive identification of risk and protective variants that contribute significantly to any common disease of interest. Toward this end, we will: * Create a Common Disease Consortium (CDC) that brings together a collaborative network of investigators with deep clinical and genetic expertise and >1.1 million well-characterized samples (cases and controls) across diverse populations, including Europeans, African Americans, Hispanics and Asians. The CDC will undertake genetic studies under three major projects related to: (1) Five systemic diseases - early-onset coronary artery disease, type 2 diabetes, inflammatory bowel disease, atrial fibrillation, and stroke; (2) Three severe neurological disorders - autism, schizophrenia and epilepsy; and (3) Two countries with special advantages for genetic studies - Finland and Estonia. Through these three projects, the CDC will explore a range of study designs, population-genetic strategies, genetic architectures, and diverse populations. * Sequence 450,000 samples from the CDC, using the expertise of the Broad Institute's genomics platform to generate high quality data and to drive down sequencing costs. Analyze the sequence data to elucidate the genetic basis of the diseases, by applying state- of-the-art methods from in our preliminary studies and developing new methods to increase power to detect association. Create, disseminate and share data, tools, and resources, to enable the scientific community to access and analyze genetic studies from the CDC and other sources.

Public Health Relevance

We aim to develop, apply and test a powerful, reliable and general strategy for 'comprehensive' identification of risk and protective variants that contribute significantly to common diseases. Toward this end, we have assembled a Common Disease Consortium (including >1,100,000 samples from cases and controls for nine diseases and participants from two unusual national biobanks). We aim to sequence and analyze DNA and phenotypes from 450,000 samples, as well as to improve methods for sequencing and analysis.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
3UM1HG008895-01S1
Application #
9316816
Study Section
Program Officer
Felsenfeld, Adam
Project Start
2016-01-14
Project End
2019-11-30
Budget Start
2016-08-05
Budget End
2016-11-30
Support Year
1
Fiscal Year
2016
Total Cost
$6,200,000
Indirect Cost
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Khera, Amit V; Emdin, Connor A; Drake, Isabel et al. (2016) Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med 375:2349-2358