Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population

被引:17
|
作者
Tangtanatakul, Pattarin [1 ]
Thumarat, Chisanu [2 ]
Satproedprai, Nusara [3 ]
Kunhapan, Punna [3 ]
Chaiyasung, Tassamonwan [3 ]
Klinchanhom, Siriwan [4 ]
Wang, Yong-Fei [5 ,6 ]
Wei, Wei [7 ,8 ]
Wongshinsri, Jeerapat [9 ]
Chiewchengchol, Direkrit [4 ]
Rodsaward, Pongsawat [4 ]
Ngamjanyaporn, Pintip [10 ]
Suangtamai, Thanitta [10 ]
Mahasirimongkol, Surakameth [3 ]
Pisitkun, Prapaporn [2 ]
Hirankarn, Nattiya [4 ]
机构
[1] Chulalongkorn Univ, Fac Allied Hlth Sci, Dept Transfus Sci & Clin Microbiol, Bangkok, Thailand
[2] Mahidol Univ, Ramathibodi Hosp, Fac Med, Sect Translat Med, Bangkok, Thailand
[3] Minist Publ Hlth, Dept Med Sci, Nonthaburi, Thailand
[4] Chulalongkorn Univ, Fac Med, Ctr Excellent Immunol & Immune Mediated Dis, Dept Microbiol, 1873 Ratchadamri Rd, Bangkok 10330, Thailand
[5] Univ Hong Kong, Fac Med, Dept Paediat & Adolescent Med, Sandy Bay, 21 Sassoon Rd, Hong Kong, Peoples R China
[6] Shenzhen Futian Hosp Rheumat Dis, Shenzhen, Peoples R China
[7] Jining Med Univ, Affiliated Hosp, Lupus Res Inst, Jining, Peoples R China
[8] Jining Med Univ, Collaborat Innovat Ctr Birth Defect Res & Transfo, Jining, Peoples R China
[9] Nopparat Rajathanee Hosp, Dept Med, Bangkok, Thailand
[10] Mahidol Univ, Ramathibodi Hosp, Fac Med, Div Allergy Immunol & Rheumatol,Dept Med, Bangkok, Thailand
基金
中国国家自然科学基金;
关键词
Genome-wide association study; Thai population; Systemic lupus erythematosus; Genetic susceptibility; Single nucleotide polymorphisms; Polygenic risk score; GENETIC RISK SCORE; GENOTYPE IMPUTATION; SLE SUSCEPTIBILITY; CHINESE; DISEASE; POLYMORPHISMS; REPLICATION; NEPHRITIS; ITGAM; ALPHA;
D O I
10.1186/s13075-020-02276-y
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Differences in the expression of variants across ethnic groups in the systemic lupus erythematosus (SLE) patients have been well documented. However, the genetic architecture in the Thai population has not been thoroughly examined. In this study, we carried out genome-wide association study (GWAS) in the Thai population. Methods Two GWAS cohorts were independently collected and genotyped: discovery dataset (487 SLE cases and 1606 healthy controls) and replication dataset (405 SLE cases and 1590 unrelated disease controls). Data were imputed to the density of the 1000 Genomes Project Phase 3. Association studies were performed based on different genetic models, and pathway enrichment analysis was further examined. In addition, the performance of disease risk estimation for individuals in Thai GWAS was assessed based on the polygenic risk score (PRS) model trained by other Asian populations. Results Previous findings on SLE susceptible alleles were well replicated in the two GWAS. The SNPs on HLA class II (rs9270970, A>G, OR = 1.82,pvalue = 3.61E-26),STAT4(rs7582694, C>G, OR = 1.57,pvalue = 8.21E-16),GTF2I(rs73366469, A>G, OR = 1.73,pvalue = 2.42E-11), andFAM167A-BLKallele (rs13277113, A>G, OR = 0.68,pvalue = 1.58E-09) were significantly associated with SLE in Thai population. Meta-analysis of the two GWAS identified a novel locus at theFBN2that was specifically associated with SLE in the Thai population (rs74989671, A>G, OR = 1.54,pvalue = 1.61E-08). Functional analysis showed that rs74989671 resided in a peak of H3K36me3 derived from CD14+ monocytes and H3K4me1 from T lymphocytes. In addition, we showed that the PRS model trained from the Chinese population could be applied in individuals of Thai ancestry, with the area under the receiver-operator curve (AUC) achieving 0.76 for this predictor. Conclusions We demonstrated the genetic architecture of SLE in the Thai population and identified a novel locus associated with SLE. Also, our study suggested a potential use of the PRS model from the Chinese population to estimate the disease risk for individuals of Thai ancestry.
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页数:13
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