Chronic lower respiratory disease (CLRD) is the third leading cause of death globally and in the United States, and consist of chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, asthma and more rare entities. Both environmental factors ? such as smoking and air pollution ? and genetic factors are known to contribute to CLRD risk. However, poor understanding of the causal molecular mechanisms remains an obstacle in the path towards discovery of disease-modifying treatments for CLRD. In this project we will use ?omics data from the Multi-Ethnic Study of Atherosclerosis (MESA) ?cohort to build a map of genetic variants associating to epigenetic, transcriptomic, and metabolomics traits genome-wide. Linking these data, as well as other existing catalogs of genetic regulatory variants, to genetic associations to CLRD will elucidate molecular changes that underlie these diseases. Furthermore, we will analyze gene-environment interactions affecting genetic regulatory variants at the molecular level, and analyze its contribution to CLRD risk, analyzing the excellent CLRD phenotype data in the MESA Lung Study.

Public Health Relevance

In this project, we take full advantage of the unique strengths of the MESA cohort phenotype and multi-assay TOPMed genomic data to advance understanding of causal molecular processes and treatment discovery for chronic lower respiratory disease (CLRD), the third-leading cause of death. We achieve this by mapping genetic variants and gene-environment interactions that affect gene regulation, followed by analysis of their contribution to genetic associations with CLRD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL142028-02
Application #
9673216
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Gan, Weiniu
Project Start
2018-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2021-04-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biochemistry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032