期刊
NATURE GENETICS
卷 49, 期 3, 页码 438-443出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3786
关键词
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资金
- Intramural Research Programs of the National Human Genome Research Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Fellowship for Japanese Biomedical and Behavioral Researchers at the NIH from the Japan Society for the Promotion of Science Research
- Japan Foundation for Applied Enzymology
- Japan Society for the Promotion of Science [26713036]
- Kanae Foundation for the Promotion of Medical Science
- Takeda Science Foundation
- SENSHIN Medical Research Foundation
- Yokohama Foundation for Advancement of Medical Science
- Portuguese Fundacao para a Ciencia e a Tecnologia (Investigator-FCT) [CMUP-ERI/TPE/0028/2013, SFRH/BPD/70008/2010]
- Research Committee of the Tehran University of Medical Sciences [132/714]
- Grants-in-Aid for Scientific Research [26713036] Funding Source: KAKEN
- Fundação para a Ciência e a Tecnologia [CMUP-ERI/TPE/0028/2013] Funding Source: FCT
We analyzed 1,900 Turkish Behcet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL18, IRF8, and CEBPB-PTPN1, with genomewide significance (P < 5 x 10(-8)) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta analysis additionally identified R1PK2 and LACC1. The disease associated allele of rs4402765, the lead marker at 11.1A-ILIB, was associated with both decreased IL-1 alpha and increased IL-1 beta production. ABO non-secretor genotypes for two ancestry specific FUT2 SNPs showed strong disease association (P = 5.89 x 10(-15)). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behcet's disease susceptibility.
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