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 â '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.
| Original language | English |
|---|---|
| Pages (from-to) | 323-330 |
| Number of pages | 8 |
| Journal | Nature Genetics |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-03-2016 |
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All Science Journal Classification (ASJC) codes
- Genetics
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High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry. / Sun, Celi; Molineros, Julio E.; Looger, Loren L.; Zhou, Xu Jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan Yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So Young; Lee, Hye Soon; Kim, Tae Hwan; Kang, Young Mo; Suh, Chang Hee; Chung, Won Tae; Park, Yong Beom; Choe, Jung Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin Seok; Kim, Young Jin; Han, Bok Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M.; Wren, Jonathan D.; Harley, John B.; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang Cheol; Nath, Swapan K.
In: Nature Genetics, Vol. 48, No. 3, 01.03.2016, p. 323-330.Research output: Contribution to journal › Article
TY - JOUR
T1 - High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry
AU - Sun, Celi
AU - Molineros, Julio E.
AU - Looger, Loren L.
AU - Zhou, Xu Jie
AU - Kim, Kwangwoo
AU - Okada, Yukinori
AU - Ma, Jianyang
AU - Qi, Yuan Yuan
AU - Kim-Howard, Xana
AU - Motghare, Prasenjeet
AU - Bhattarai, Krishna
AU - Adler, Adam
AU - Bang, So Young
AU - Lee, Hye Soon
AU - Kim, Tae Hwan
AU - Kang, Young Mo
AU - Suh, Chang Hee
AU - Chung, Won Tae
AU - Park, Yong Beom
AU - Choe, Jung Yoon
AU - Shim, Seung Cheol
AU - Kochi, Yuta
AU - Suzuki, Akari
AU - Kubo, Michiaki
AU - Sumida, Takayuki
AU - Yamamoto, Kazuhiko
AU - Lee, Shin Seok
AU - Kim, Young Jin
AU - Han, Bok Ghee
AU - Dozmorov, Mikhail
AU - Kaufman, Kenneth M.
AU - Wren, Jonathan D.
AU - Harley, John B.
AU - Shen, Nan
AU - Chua, Kek Heng
AU - Zhang, Hong
AU - Bae, Sang Cheol
AU - Nath, Swapan K.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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 â '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.
AB - 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 â '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.
UR - http://www.scopus.com/inward/record.url?scp=84959530680&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959530680&partnerID=8YFLogxK
U2 - 10.1038/ng.3496
DO - 10.1038/ng.3496
M3 - Article
C2 - 26808113
AN - SCOPUS:84959530680
VL - 48
SP - 323
EP - 330
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -