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.However, linking these intergenic or intronic GWAS regions to the correct disease casual genes relies on deep understanding on the chromatin states and chromatin interaction map in relevant lung cell types. We apply different types of ”Cs” methods (including 3C and 4C, capture HiC et al) in lung-derived epithelial and fibroblasts to assign correct genes into the COPD GWAS regions. We also assess genome-wide DNA accessibility by ATAC-Seq (transposase-accessible chromatin using sequencing) and DNase-Seq in important lung cell types including epithelial and fibroblasts. We subsequently apply CRISPR/Cas9-based genome editing method to confirm impacts of these regulatory elements within GWAS regions on gene expression levels in human bronchial epithelial cells.

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