Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death in the U.S. It is characterized by thickening of the airway wall and emphysematous destruction in distal lungs. Despite smoking is the major risk for COPD, a substantial portion of differences in COPD susceptibility are due to genetic factors, with an estimated heritability of ~25-60%. Genome-wide association studies (GWAS) have identified susceptibility loci for many complex diseases including COPD. However, in-depth functional and mechanistic studies targeting GWAS candidate genes in the post-GWAS era have been relatively limited. To address this, we will:
1) link GWAS genetic variants to disease causal genes;
2) identify functional variants within GWAS regions;
3) determine function of these novel GWAS genes in murine models;
4) connect these seemingly isolated new genes by shared signaling pathways important for lung homeostasis.
We thanks funding supports from NIH National Heart, Lung, and Blood Institute R01HL147148; P01HL132825; R01HL137927; R01HL148667; R01HL127200; R01HL152728; P01HL114501; R01HL118455.
Link GWAS Variants to Novel Disease Genes
More than 50% of GWAS regions identified in complex traits are located in the non-coding regions of human genome, indicating potential regulatory roles of these functional variants. More>>
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