1. Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations.
- Author
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Zhang Y, Yang J, Zhang J, Sun L, Hirankarn N, Pan HF, Lau CS, Chan TM, Lee TL, Leung AM, Mok CC, Zhang L, Wang Y, Shen JJ, Wong SN, Lee KW, Ho MH, Lee PP, Chung BH, Chong CY, Wong RW, Mok MY, Wong WH, Tong KL, Tse NK, Li XP, Avihingsanon Y, Rianthavorn P, Deekajorndej T, Suphapeetiporn K, Shotelersuk V, Ying SK, Fung SK, Lai WM, Wong CM, Ng IO, Garcia-Barcelo MM, Cherny SS, Cui Y, Sham PC, Yang S, Ye DQ, Zhang XJ, Lau YL, and Yang W
- Subjects
- Adult, Case-Control Studies, Female, Gene Expression Regulation genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Oncogene Proteins, Fusion genetics, Polymorphism, Single Nucleotide, Tetraspanins, fas Receptor genetics, 5-Lipoxygenase-Activating Proteins genetics, Asian People genetics, B7-1 Antigen genetics, Epistasis, Genetic genetics, Lupus Erythematosus, Systemic genetics
- Abstract
Objectives: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility., Methods: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction., Results: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets., Conclusions: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
- Published
- 2016
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