Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy

• Published in: Nature genetics Vol. 47; no. 3; pp. 267 - 271
• Main Authors: Liu, Hong, Irwanto, Astrid, Fu, Xi'an, Yu, Gongqi, Yu, Yongxiang, Sun, Yonghu, Wang, Chuan, Wang, Zhenzhen, Okada, Yukinori, Low, Huiqi, Li, Yi, Liany, Herty, Chen, Mingfei, Bao, Fangfang, Li, Jinghui, You, Jiabao, Zhang, Qilin, Liu, Jian, Chu, Tongsheng, Andiappan, Anand Kumar, Wang, Na, Niu, Guiye, Liu, Dianchang, Yu, Xiulu, Zhang, Lin, Tian, Hongqing, Zhou, Guizhi, Rotzschke, Olaf, Chen, Shumin, Zhang, Xuejun, Liu, Jianjun, Zhang, Furen
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2015; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 692/699/255/1318; Adult; Aged; Agriculture; Animal Genetics and Genomics; Asian Continental Ancestry Group - genetics; Autoimmunity - genetics; Bacterial infections; Bioinformatics; Biomedicine; Cancer Research; Case-Control Studies; Datasets; Disease susceptibility; Female; Gene Function; Genealogy; Genetic aspects; Genetic factors; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study - methods; Genomes; Genomics; Health aspects; Human Genetics; Humans; Infections; Inflammation - genetics; Leprosy; Leprosy - genetics; letter; Male; Middle Aged; Mycobacteria; Mycobacterium; Polymorphism, Single Nucleotide; Risk Factors; Software; Statistical analysis; United States; China
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3212

Furen Zhang and colleagues report the results of a three-stage genome-wide association study of leprosy in the Chinese population. They discover six new susceptibility loci and observe substantial overlap with loci previously implicated in autoimmune and inflammatory diseases. 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.