Journal
NATURE GENETICS
Volume 48, Issue 3, Pages 323-330Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3496
Keywords
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Categories
Funding
- Korea Center for Disease Control and Prevention at the Korea National Institute of Health
- Ministry of Health and Welfare, Republic of Korea
- US National Institutes of Health [AR060366, MD007909, AI103399, AI024717, AI083194, AI107176, TR001425, HG008666, HG006828]
- US Department of Defense [PR094002]
- US Department of Veterans Affairs
- National Basic Research Program of China (973 program) [2014CB541902]
- Research Fund of Beijing Municipal Science and Technology for the Outstanding PhD Program [20121000110]
- National Natural Science Foundation of China [81200524, 81230072]
- High-Impact Research Ministry of Education, Malaysia [UM.C/625/1/HIR/MoE/E000044-20001]
- Korea Healthcare Technology RAMP
- D Project, Ministry for Health and Welfare, Republic of Korea [HI13C2124]
- Korea Center for Disease Control and Prevention at the Korea National Institute of Health
- Ministry of Health and Welfare, Republic of Korea
- US National Institutes of Health [AR060366, MD007909, AI103399, AI024717, AI083194, AI107176, TR001425, HG008666, HG006828]
- US Department of Defense [PR094002]
- US Department of Veterans Affairs
- National Basic Research Program of China (973 program) [2014CB541902]
- Research Fund of Beijing Municipal Science and Technology for the Outstanding PhD Program [20121000110]
- National Natural Science Foundation of China [81200524, 81230072]
- High-Impact Research Ministry of Education, Malaysia [UM.C/625/1/HIR/MoE/E000044-20001]
- Korea Healthcare Technology RAMP
- D Project, Ministry for Health and Welfare, Republic of Korea [HI13C2124]
- Grants-in-Aid for Scientific Research [15H05911, 15H05670, 25293225] Funding Source: KAKEN
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Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRDI-GTF21 at 7q11.23 (rs73366469, P-meta = 3.75 x 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL128, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.
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