Genome‐wide meta‐analysis and fine‐mapping prioritize potential causal variants and genes related to leprosy
Zhenzhen Wang,
Tingting Liu,
Wenchao Li,
Gongqi Yu,
Zihao Mi,
Chuan Wang,
Xiaojie Liao,
Pengcheng Huai,
Tongsheng Chu,
Dianchang Liu,
Lele Sun,
Xi'an Fu,
Yonghu Sun,
Honglei Wang,
Na Wang,
Jianjun Liu,
Hong Liu,
Furen Zhang
Affiliations
Zhenzhen Wang
Department of Biostatistics School of Public Health Cheeloo College of Medicine Shandong University Jinan Shandong China
Tingting Liu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Wenchao Li
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Gongqi Yu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Zihao Mi
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Chuan Wang
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Xiaojie Liao
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Pengcheng Huai
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Tongsheng Chu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Dianchang Liu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Lele Sun
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Xi'an Fu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Yonghu Sun
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Honglei Wang
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Na Wang
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Jianjun Liu
Department of Human Genetics, Genome Institute of SingaporeSingaporeSingapore
Hong Liu
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Furen Zhang
Shandong Provincial Key Lab for Dermatovenereology, Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences Jinan Shandong China
Abstract 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.