984 Genome-wide meta-analysis and fine mapping prioritize potential causal variants and genes for leprosy

Genome-wide association studies (GWAS) have discovered 35 susceptible leprosy loci, but the cumulative effects of these loci can only partially explain overall risk leprosy, and causal variants genes within remain to be clarified. Here we performed a meta-GWAS analysis in two newly generated (5,007 cases 4,579 controls) multiple previously published (2,277 3,159 datasets. Four novel 14 reported were identified. A comprehensive fine-mapping strategy was conducted out, 20 (eight protein-damaging 12 regulatory variants) 16 nominated. The biological annotation revealed variants, especially locus chr12:57,665,085 - 58,665,085 CSK, located immune-relevant or immune-specific elements. Our study highlighted key roles immune related tissues, cells implicated PD-1 pathways pathogenesis leprosy. identifies candidate elucidates potential coding mechanisms for underlying