High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry
| Autor: | Xana Kim-Howard, Takayuki Sumida, Celi Sun, Hong Zhang, Bok Ghee Han, Chang Hee Suh, Yong Beom Park, So Young Bang, Swapan K. Nath, Kwangwoo Kim, Nan Shen, Young Mo Kang, Kek Heng Chua, Yukinori Okada, Jonathan D. Wren, Yuan-yuan Qi, Julio E. Molineros, Akari Suzuki, Xu-jie Zhou, Seung Cheol Shim, Loren L. Looger, Sang Cheol Bae, Michiaki Kubo, John B. Harley, Adam Adler, Jung Yoon Choe, Hye Soon Lee, Young-Jin Kim, Kazuhiko Yamamoto, Prasenjeet Motghare, Yuta Kochi, Won Tae Chung, Kenneth M. Kaufman, Mikhail G. Dozmorov, Shin-Seok Lee, Tae-Hwan Kim, Jianyang Ma, Krishna Bhattarai |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Genotype Genotyping Techniques CD226 Gene Expression Locus (genetics) Genome-wide association study Biology Polymorphism Single Nucleotide Article White People 03 medical and health sciences Asian People Genetics medicine Humans Lupus Erythematosus Systemic Genetic Predisposition to Disease Genotyping Lupus erythematosus medicine.disease Genetic architecture 3. Good health 030104 developmental biology Female Genome-Wide Association Study |
| Zdroj: | Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | 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, Pmeta = 3.75 × 10(-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. |
| Databáze: | OpenAIRE |
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