title: Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.
abstract: Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases.
authors: 1] Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China. [2] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [3] School of Medicine, Shandong University, Jinan, China. [4] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Hong
authors: H
authors: Liu
authors: 1] Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore. [2] Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors: Astrid
authors: A
authors: Irwanto
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Xi'an
authors: X
authors: Fu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Gongqi
authors: G
authors: Yu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Yongxiang
authors: Y
authors: Yu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Yonghu
authors: Y
authors: Sun
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Chuan
authors: C
authors: Wang
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Zhenzhen
authors: Z
authors: Wang
authors: 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
authors: Yukinori
authors: Y
authors: Okada
authors: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore.
authors: Huiqi
authors: H
authors: Low
authors: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore.
authors: Yi
authors: Y
authors: Li
authors: Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore.
authors: Herty
authors: H
authors: Liany
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Mingfei
authors: M
authors: Chen
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Fangfang
authors: F
authors: Bao
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Jinghui
authors: J
authors: Li
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Jiabao
authors: J
authors: You
authors: School of Medicine, Shandong University, Jinan, China.
authors: Qilin
authors: Q
authors: Zhang
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Jian
authors: J
authors: Liu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Tongsheng
authors: T
authors: Chu
authors: Singapore Immunology Network, Singapore.
authors: Anand Kumar
authors: AK
authors: Andiappan
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Na
authors: N
authors: Wang
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Guiye
authors: G
authors: Niu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Dianchang
authors: D
authors: Liu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Xiulu
authors: X
authors: Yu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Lin
authors: L
authors: Zhang
authors: 1] Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China. [2] National Clinical Key Project of Dermatology and Venereology, Jinan, China.
authors: Hongqing
authors: H
authors: Tian
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Guizhi
authors: G
authors: Zhou
authors: Singapore Immunology Network, Singapore.
authors: Olaf
authors: O
authors: Rotzschke
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
authors: Shumin
authors: S
authors: Chen
authors: 1] Department of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, China. [2] Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education and Anhui Province, Hefei, China.
authors: Xuejun
authors: X
authors: Zhang
authors: 1] Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore. [2] Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors: Jianjun
authors: J
authors: Liu
authors: 1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] School of Medicine, Shandong University, Jinan, China. [3] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China. [4] National Clinical Key Project of Dermatology and Venereology, Jinan, China.
authors: Furen
authors: F
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007918:Leprosy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors