scholarly journals Fine-Mapping of the Major Histocompatibility Complex Region Linked to Leprosy in Northern China

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruixue Zhang ◽  
Lu Cao ◽  
Weiwei Chen ◽  
Huiyao Ge ◽  
Xia Hu ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Fine Mapping ◽  
Complex Traits ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Genome Project ◽  
Han Chinese ◽  
Major Histocompatibility ◽  
Han Chinese Population ◽  
Histocompatibility Complex

Background: Leprosy is a chronic infectious skin and neurological disease, and genetic background is considered to be one of the major factors of risk. The major histocompatibility complex (MHC) region not only affects susceptibility to leprosy but also its development and outcome. Given the complex traits of the MHC region, variants and the potential mechanism by which HLA influences leprosy development need to be further explored.Methods: We extracted previous genome-wide association study data from the Northern Han Chinese population to perform HLA fine-mapping. Using the 1,000 Genome Project Phase 3 dataset as the reference panel, single-nucleotide polymorphisms (SNP), insertion and deletion (INDEL) and copy number variant (CNV) imputation were carried out. HLA classical alleles and amino acids in the MHC region were imputed using the HAN-MHC database. Further stepwise regression analysis was conducted to analyze independent signals of variants related to leprosy.Results: We identified four independent variants: esv3608598, rs7754498, rs3130781 and rs144388449. Among them, esv3608598 is a CNV and the first HLA CNV associated with leprosy risk. SNP annotation using RegulomeDB, HaploReg, and rVarBase showed that three SNPs are likely to affect the pathogenesis of leprosy.Conclusion: In summary, this is the first study to assess the association between HLA CNV and leprosy susceptibility in a Northern Han Chinese population. By fine mapping of the MHC region in this population, our findings provide evidence for the contribution of HLA to leprosy susceptibility.

scholarly journals A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians

2006 ◽  
Vol 13 (4) ◽  
pp. 489-498 ◽  
Author(s):  
Hsin-Chou Yang ◽  
Chien-Hsin Lin ◽  
Chia-Ling Hsu ◽  
Shuen-Iu Hung ◽  
Jer-Yuan Wu ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Han Chinese ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population

2019 ◽  
Author(s):  
Sijia Zhang ◽  
Esma Jamaspishvili ◽  
Huixin Tong ◽  
Yongjie Chen ◽  
Zhongyu Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
East Asian ◽  
Repetitive Sequences ◽  
Han Chinese ◽  
Han Chinese Population ◽  
Genome Wide

Meta-analysis of GWAS in East Asian populations had established 10 loci that were associated with type 2 diabetes. Eight of them were with genome-wide significance and two with a border line association. Since these data have not been studied in an independent Han Chinese population, we aimed to investigate the association of these susceptibility loci with type 2 diabetes in an independent Han Chinese population. We executed a case-control study in 2 000 Chinese by the SNPscan method. Firstly, the repetitive sequences of 10 loci were assessed. Next, we investigated the association of 8 SNPs out of 10 with type 2 diabetes and constructed the GRS of those 8 SNPs. Finally, the relationship of the 8 loci and diabetes-related traits was analyzed. Based on the fact, that highly repetitive sequences were detected in 2 SNPs, we investigated the remaining 8 SNPs. With the exception of four SNPs (CMIP rs16955379, PEPD rs3786897, PSMD6 rs831571, ZFAND3 rs9470794), the other SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports, especially GLIS3 rs7041847 and KCNK16 rs1535500 were significantly associated with type 2 diabetes (rs1535500: p=0.005, OR=1.224, 95% CI 1.062–1.409; rs7041847: p=0.035, OR=1.118, 95% CI 1.070–1.388). The GRS constructed from the 8 SNPs was significantly associated with type 2 diabetes in the Chinese population (p=0.004, OR=1.065, 95% CI: 1.021–1.111). Among the participants with 24≤BMI<28 kg/m2 the 8 SNPs were significantly associated with type 2 diabetes (p=0.040, OR=1.079, 95% CI: 1.003–1.160). In quantitative trait analyses, WWOX rs17797882 was associated with decreased HOMA-β and increased level of TG and HDL-Ch, while PEPD rs3786897 and MAEA rs6815464 were associated with decreased fasting plasma glucose, and KCNK16 rs1535500 has shown a significant association with increased T-Ch and PSMD6 rs831571 had a significant association with decreased HDL-Ch. In Conclusion, with high probability the 8 loci identified in the East Asian GWAS meta-analysis are associated with type 2 diabetes in the Han Chinese population.

scholarly journals Fine Mapping Major Histocompatibility Complex Associations in Psoriasis and Its Clinical Subtypes

2014 ◽  
Vol 95 (2) ◽  
pp. 162-172 ◽  
Author(s):  
Yukinori Okada ◽  
Buhm Han ◽  
Lam C. Tsoi ◽  
Philip E. Stuart ◽  
Eva Ellinghaus ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Fine Mapping ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Association between Ocular Axial Length-Related Genes and High Myopia in a Han Chinese Population

2015 ◽  
Vol 235 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Ya-Ting Li ◽  
Ming-Kun Xie ◽  
Jin Wu
Keyword(s):  
Axial Length ◽  
Genetic Variants ◽  
Chinese Population ◽  
High Myopia ◽  
Genome Wide Association Study ◽  
Han Chinese ◽  
Nucleotide Polymorphisms ◽  
Han Chinese Population ◽  
Functional Roles ◽  
Genome Wide

Aims: A previous genome-wide association study of high myopia identified five genome-wide loci for ocular axial length (C3orf26, ZC3H11B, RSPO1, GJD2, and ZNRF3). The aim of our study was to investigate the association between high myopia and genetic variants in the five loci in Han Chinese subjects. Methods: Five single nucleotide polymorphisms were genotyped in 296 unrelated high-myopia subjects and 300 matched emmetropic controls by the SNaPshot method. The distribution of genotypes in the cases and controls was compared in codominant, dominant, and recessive genetic models by using SNPStats online software. Results: Significant associations between rs994767 near ZC3H11B (p = 0.001), rs4074961 in RSPO1 (p < 0.001), and rs11073058 in GJD2 (p = 0.029) and high myopia were observed. Odds ratios (95% confidence intervals) were 1.532 (1.200-1.955), 1.603 (1.267-2.029), and 1.290 (1.027-1.621) for the rs994767 T allele, rs4074961 T allele, and rs11073058 T allele, respectively. But rs9811920 in C3orf26 and rs12321 in ZNRF3 were not associated with high myopia. Conclusion: Our findings suggested that genetic variants in ZC3H11B, RSPO1, and GJD2 are associated with susceptibility to the development of high myopia in a Han Chinese population. Functional roles of ZC3H11B, RSPO1, and GJD2 in the pathology of high myopia need to be further investigated.

Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

2011 ◽  
Vol 70 (10) ◽  
pp. 1793-1797 ◽  
Author(s):  
Patrick Danoy ◽  
Meng Wei ◽  
Hadler Johanna ◽  
Lei Jiang ◽  
Dongyi He ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Study ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Two Phase ◽  
Han Chinese Population

BackgroundThe genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations.ObjectiveTo investigate these associations in the Han Chinese population.MethodsHaplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2=0.8) across 19 distinct RA genomic regions. A two phase case–control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied.ResultsRobust association was detected for MMEL1 and CTLA4, and modest association was identified for another six loci: PADI4, STAT4, PRDM1, CDK6, TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10−5 unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4, significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10−5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed.ConclusionThis study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

scholarly journals Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes

2021 ◽  
pp. annrheumdis-2021-219884
Author(s):  
Marialbert Acosta-Herrera ◽  
Martin Kerick ◽  
Elena Lopéz-Isac ◽  
Shervin Assassi ◽  
Lorenzo Beretta ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Systemic Sclerosis ◽  
Genome Wide Association Study ◽  
Genetic Effect ◽  
Nucleotide Polymorphisms ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Genome Wide ◽  
Novel Association ◽  
Hla Dqa1

ObjectiveThe greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes.Methods9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues. Additionally, patients were stratified according to their clinical and serological status, namely, limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), anticentromere (ACA), antitopoisomerase (ATA) and anti-RNApolIII autoantibodies (ARA).ResultsSequential conditional analyses showed nine SNPs, nine classical alleles and seven amino acids that modelled the observed associations with SSc. This confirmed previously reported associations with HLA-DRB1*11:04 and HLA-DPB1*13:01, and revealed a novel association of HLA-B*08:01. Stratified analyses showed specific associations of HLA-DQA1*02:01 with lcSSc, and an exclusive association of HLA-DQA1*05:01 with dcSSc. Similarly, private associations were detected in HLA-DRB1*08:01 and confirmed the previously reported association of HLA-DRB1*07:01 with ACA-positive patients, as opposed to the HLA-DPA1*02:01 and HLA-DQB1*03:01 alleles associated with ATA presentation.ConclusionsThis study confirms the contribution of HLA class II and reveals a novel association of HLA class I with SSc, suggesting novel pathways of disease pathogenesis. Furthermore, we describe specific HLA associations with SSc clinical and serological subtypes that could serve as biomarkers of disease severity and progression.

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