Journal
HUMAN MOLECULAR GENETICS
Volume 23, Issue 2, Pages 524-533Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt424
Keywords
-
Funding
- S Kee Yee Medical Foundation [211203]
- Research Grant Council of the Hong Kong Government [GRFHKU783813M, HKU781709M, HKU784611M, HKU 770411M]
- MOE of China [IRT-1046]
- National Natural Science Foundation of China [81171505, 30972727, 30830089]
- State Key Basic Research Program 973 of China [2011CB512103, 2012CB722404]
- National Research University Project of CHE
- Ratchadaphiseksomphot Endowment Fund [HR1163A]
- National Research Council of Thailand
- Thailand Research Fund
Ask authors/readers for more resources
Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P_(combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P_(combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P_(combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available