@article{b86bcccc6346404cba81f833a48afa02,
title = "High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry",
abstract = "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 GTF2IRD1-GTF2I at 7q11.23 (rs73366469, P meta = 3.75 × 10 {\^a} '117, odds ratio (OR) = 2.38), followed by DEF6, IL12B, 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.",
author = "Celi Sun and Molineros, {Julio E.} and Looger, {Loren L.} and Zhou, {Xu Jie} and Kwangwoo Kim and Yukinori Okada and Jianyang Ma and Qi, {Yuan Yuan} and Xana Kim-Howard and Prasenjeet Motghare and Krishna Bhattarai and Adam Adler and Bang, {So Young} and Lee, {Hye Soon} and Kim, {Tae Hwan} and Kang, {Young Mo} and Suh, {Chang Hee} and Chung, {Won Tae} and Park, {Yong Beom} and Choe, {Jung Yoon} and Shim, {Seung Cheol} and Yuta Kochi and Akari Suzuki and Michiaki Kubo and Takayuki Sumida and Kazuhiko Yamamoto and Lee, {Shin Seok} and Kim, {Young Jin} and Han, {Bok Ghee} and Mikhail Dozmorov and Kaufman, {Kenneth M.} and Wren, {Jonathan D.} and Harley, {John B.} and Nan Shen and Chua, {Kek Heng} and Hong Zhang and Bae, {Sang Cheol} and Nath, {Swapan K.}",
note = "Funding Information: We are grateful to the affected and unaffected individuals who participated in this study. We thank the research assistants, coordinators and physicians who helped in the recruitment of subjects, including the individuals in the coordinating projects. A part of the Korean control data was provided from the Korean Biobank Project supported by the Korea Center for Disease Control and Prevention at the Korea National Institute of Health. Genomic DNA from ~100 Korean patients with SLE was obtained from the Korean National Biobank at Wonkwang University Hospital, which is supported by the Ministry of Health and Welfare, Republic of Korea. This work was supported by grants from the US National Institutes of Health (AR060366, MD007909, AI103399, AI024717, AI083194, AI107176, TR001425, HG008666 and HG006828), the US Department of Defense (PR094002), the US Department of Veterans Affairs, the National Basic Research Program of China (973 program) (2014CB541902), the Research Fund of Beijing Municipal Science and Technology for the Outstanding PhD Program (20121000110), the National Natural Science Foundation of China (81200524, 81230072) and High-Impact Research Ministry of Education Grant UM.C/625/1/HIR/MoE/E000044-20001, Malaysia. This study was also supported by a grant from the Korea Healthcare Technology R&D Project (HI13C2124), Ministry for Health and Welfare, Republic of Korea. Funding Information: We are grateful to the affected and unaffected individuals who participated in this study. We thank the research assistants, coordinators and physicians who helped in the recruitment of subjects, including the individuals in the coordinating projects. A part of the Korean control data was provided from the Korean Biobank Project supported by the Korea Center for Disease Control and Prevention at the Korea National Institute of Health. Genomic DNA from ~100 Korean patients with SLE was obtained from the Korean National Biobank at Wonkwang University Hospital, which is supported by the Ministry of Health and Welfare, Republic of Korea. This work was supported by grants from the US National Institutes of Health (AR060366, MD007909, AI103399, AI024717, AI083194, AI107176, TR001425, HG008666 and HG006828), the US Department of Defense (PR094002), the US Department of Veterans Affairs, the National Basic Research Program of China (973 program) (2014CB541902), the Research Fund of Beijing Municipal Science and Technology for the Outstanding PhD Program (20121000110), the National Natural Science Foundation of China (81200524, 81230072) and High-Impact Research Ministry of Education Grant UM.C/625/1/HIR/MoE/E000044-20001, Malaysia. This study was also supported by a grant from the Korea Healthcare Technology R&D Project (HI13C2124), Ministry for Health and Welfare, Republic of Korea.",
year = "2016",
month = mar,
day = "1",
doi = "10.1038/ng.3496",
language = "English",
volume = "48",
pages = "323--330",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}