02366nas a2200409   4500000000100000008004100001260001200042653001900054653003600073653002000109653001200129653002100141100001100162700001000173700000900183700000900192700000900201700001100210700001100221700001100232700001000243700001000253700001000263700000900273700001000282700001100292700001100303700001000314700001000324700001200334245011400346856007800460300000900538490000600547520138900553022001401942       2023                            d  c12/202310afine‐mapping10agenome‐wide association study10aImmune response10aleprosy10apathway analysis1 aWang Z1 aLiu T1 aLi W1 aYu G1 aMi Z1 aWang C1 aLiao X1 aHuai P1 aChu T1 aLiu D1 aSun L1 aFu X1 aSun Y1 aWang H1 aWang N1 aLiu J1 aLiu H1 aZhang F00aGenome-wide meta-analysis and fine-mapping prioritize potential causal variants and genes related to leprosy.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674079/pdf/MCO2-4-e415.pdf  a1-160 v43 a<p>To date, genome-wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta-analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine-mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune-relevant or immune-specific regulatory elements. Furthermore, by using gene-set, tissue, and cell-type enrichment analyses, we highlighted the key roles of immune-related tissues and cells and implicated the PD-1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy.</p>
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