Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy

• Published in: Nature genetics Vol. 43; no. 12; pp. 1247 - 1251
• Main Authors: Zhang, Furen, Liu, Hong, Chen, Shumin, Low, Huiqi, Sun, Liangdan, Cui, Yong, Chu, Tongsheng, Li, Yi, Fu, Xi'an, Yu, Yongxiang, Yu, Gongqi, Shi, Benqing, Tian, Hongqing, Liu, Dianchang, Yu, Xiulu, Li, Jinghui, Lu, Nan, Bao, Fangfang, Yuan, Chunying, Liu, Jian, Liu, Huaxu, Zhang, Lin, Sun, Yonghu, Chen, Mingfei, Yang, Qing, Yang, Haitao, Yang, Rongde, Zhang, Lianhua, Wang, Qiang, Zuo, Fuguang, Zhang, Haizhen, Khor, Chiea Chuen, Hibberd, Martin L, Yang, Sen, Liu, Jianjun, Zhang, Xuejun
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2011; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/727/2000; 631/326/41/1470; 631/326/41/2533; Aged; Agriculture; Animal Genetics and Genomics; Bacterial diseases; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Chromosomes, Human, Pair 11; Disease; Disease susceptibility; Epistasis, Genetic; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Haplotypes; Human; Human bacterial diseases; Human Genetics; Humans; Infectious diseases; Leprosy; Leprosy - genetics; letter; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Nod2 Signaling Adaptor Protein - genetics; Pathogenesis; Polymorphism, Single Nucleotide; Population genetics, reproduction patterns; Principal Component Analysis; rab GTP-Binding Proteins - genetics; Receptor-Interacting Protein Serine-Threonine Kinase 2 - genetics; Receptors, Interleukin - genetics; Risk factors; Single nucleotide polymorphisms; Tropical bacterial diseases; Validation studies; China; Infection; Human; Skin disease; Bacteriosis; Leprosy; Chinese; Mycobacterial infection; Population genetics
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.973

Furen Zhang and colleagues report a genome-wide association study for susceptibility to leprosy. They identify two new risk loci at IL23R and RAB32 . We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10 −14 , OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10 −11 , OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.