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Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.

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

Author information

1
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.
2
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.
3
1] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [2] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.
4
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.
5
Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore.
6
School of Medicine, Shandong University, Jinan, China.
7
Singapore Immunology Network, Singapore.
8
1] Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China. [2] National Clinical Key Project of Dermatology and Venereology, Jinan, China.
9
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.
10
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.

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.

PMID:
25642632
DOI:
10.1038/ng.3212
[Indexed for MEDLINE]
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