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The chromosome 4q region harbors multiple genetic risk loci for COPD, including signals near <jats:italic>HHIP<\/jats:italic>, <jats:italic>FAM13A<\/jats:italic>, <jats:italic>GSTCD<\/jats:italic>, <jats:italic>TET2<\/jats:italic>, and <jats:italic>BTC<\/jats:italic>. Leveraging RNA-Seq data from lung tissue in COPD cases and controls, we estimated the co-expression network for genes in the 4q region bounded by <jats:italic>HHIP<\/jats:italic> and <jats:italic>BTC<\/jats:italic> (~70MB), through partial correlations informed by protein-protein interactions. We identified several co-expressed gene pairs based on partial correlations, including <jats:italic>NPNT-HHIP<\/jats:italic>, <jats:italic>BTC<\/jats:italic>-<jats:italic>NPNT<\/jats:italic> and <jats:italic>FAM13A<\/jats:italic>-<jats:italic>TET2<\/jats:italic>, which were replicated in independent lung tissue cohorts. Upon clustering the co-expression network, we observed that four genes previously associated to COPD: <jats:italic>BTC<\/jats:italic>, <jats:italic>HHIP<\/jats:italic>, <jats:italic>NPNT<\/jats:italic> and <jats:italic>PPM1K<\/jats:italic> appeared in the same network community. Finally, we discovered a sub-network of genes differentially co-expressed between COPD vs controls (including <jats:italic>FAM13A<\/jats:italic>, <jats:italic>PPA2<\/jats:italic>, <jats:italic>PPM1K<\/jats:italic> and <jats:italic>TET2)<\/jats:italic>. Many of these genes were previously implicated in cell-based knock-out experiments, including the knocking out of <jats:italic>SPP1<\/jats:italic> which belongs to the same genomic region and could be a potential local key regulatory gene. These analyses identify chromosome 4q as a region enriched for COPD genetic susceptibility and differential co-expression.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011079","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T17:37:43Z","timestamp":1729186663000},"page":"e1011079","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Partial correlation network analysis identifies coordinated gene expression within a regional cluster of COPD genome-wide association 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