Genome-wide association study of leprosy in Chinese population
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ABSTRACT:
PROVIDER: PRJNA75569 | ENA |
REPOSITORIES: ENA
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Project description:<p>Leprosy is a chronic infectious disease caused by <i>Mycobacterium leprae</i> (<i>M. leprae</i>). Due to <i>M. leprae's</i>
narrow host range and an inability to be cultured <i>in vitro</i>, the biological investigation of this disease has been difficult. Host
genetic factors have been suggested to play an important role in disease development, but few have been identified.</p>
<p>In this study, we attempted to identify the host genetic factors by performing a two-stage genome-wide association
study (GWAS) in Chinese population. The initial genome-wide scan was done by genotyping 706 patients and 1225 controls using
the Illumina HumanHap610 BeadChip, and the follow-up study was performed by genotyping 93 SNPs in three independent samples
consisting of 3254 cases and 5955 controls. We identified significant association (P<10<sup>-10</sup>) within six genes
CCDC122 (13q14), C13orf31 (13q14), NOD2 (16q12), TNFSF15 (9q32), HLA-DR (6p21) and RIPK2 (8q21), and suggestive
association (P=5.68x10<sup>-6</sup>) within LRRK2 (12q12). We also revealed suggestive evidence for C13orf31, LRRK2,
NOD2 and RIPK2 to show stronger association in the multibacillary form than the paucibacillary form of leprosy. Our
findings highlight the importance of the innate immune response, particularly NOD2-mediated signaling, in leprosy
and suggests a new therapeutic target for leprosy.</p>
<p>Here, the summary statistics from the initial genome-wide association analysis were reported.</p>
| phs000217.v1.p1 | EGA
Project description:Leprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. Genetic association studies indicated that leprosy risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but the full number of variants in this region has yet to be elucidated. To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. The meta-analysis of Chinese participants identified 10 HLA-type or amino acid variants with lower than the genome-wide significant susceptibility signal. Next, gene-by-gene step-wise conditional analysis was performed in the combined dataset of these cohorts. Finally, we identified four new independent susceptibility loci (HLA-DQA1, HLA-C, rs3129063, and rs58327373) and confirmed one previously reported locus (HLA-DRB1) that significantly associated with leprosy in the Chinese Han population. Thus the results of this study increase knowledge about leprosy risk variants and illustrate the value of HLA imputation for fine mapping of causal variants in the MHC.
2018-09-30 | GSE119367 | GEO
Project description:We perform the first two-stage GWAS on TB in the Chinese population. We examined 900,015 genetic variants in 1,008 TB patients using the HumanOmniZhongHua-8 v1.1 BeadChip.
2019-06-01 | GSE83397 | GEO
Project description:Immune thrombocytopenia (ITP) is an autoimmnue bleeding disorder characterized by low platelet count. To identify susceptibility loci for disease progression of ITP, we performed this genome-wide association study using DNA pools of 200 ITP cases and 200 controsl in Han Chinese. Performing GWAS on pools of DNA samples is an effective strategy to reduce the costs of studies and pooling DNA has been shown to be an efficient method to select candidate susceptibility loci for follow-up by individual genotyping.
2016-01-12 | GSE76744 | GEO
Project description:Genome-wide association study of leprosy in Chinese population
| PRJNA75571 | ENA
Project description:Leprosy is classified from paucibacillary leprosy (TT and BT) to multibacillary leprosy (BB, BL, and LL). In our study, we focus on selecting or classfying the significant genes to discriminate between paucibacillary and multibacillary group and the important genes to distinguish between blood and the corresponding tissue in patients.
2011-03-17 | GSE24280 | GEO
Project description:Leprosy is classified from paucibacillary leprosy (TT and BT) to multibacillary leprosy (BB, BL, and LL). In our study, we focus on selecting or classfying the significant genes to discriminate between paucibacillary and multibacillary group and the important genes to distinguish between blood and the corresponding tissue in patients. · Human Adult Normal Skin Sample (Commercial;Cat#1234218); 6 patients of leprosy (Blood and Tissue sample (Pathologic classification: BT); 6 patients of leprosy (Blood and Tissue sample (Pathologic classification: MB)) · In blood sample, BT sample vs MB sample · In tissue sample, Normal Skin sample vs tissue BT sample or tissue MB sample · Single Color Microarray · All experiments are performed one replicate
2011-03-17 | E-GEOD-24280 | biostudies-arrayexpress
Project description:Genome-wide association study of Behcet's disease in the Turkish population
| PRJNA75609 | ENA
Project description:Here we report the data generated by short-read sequencing of mRNA (polyA) isolated from granuloma annulare and leprosy skin lesions. Our main aim was to identify putative mRNA biomarkers for distinguishing leprosy from other differential diagnoses. Additionally, we also explored the distinction between MB and PB by using differential expression analysis as well as training a penalized logistic regression to select important features. Our results showed that few genes are enough to differentiate leprosy lesions, including paucibacillary cases, from other morphological and histopathological similar skin diseases. Some of these genes have been replicated in a larger and more heterogeneous sample with RT-qPCR, validating their classification potential. We also suggest important novel gene candidates to improve our understanding of molecular differences between MB and PB lesions, which could either pinpoint new pathways and targets for host-based specialized adjuvant treatment for leprosy. Finally, this dataset has been used to explore the relationship between cornification and keratinocyte-related genes and TGFB-mediated epithelial-mesenchymal transition (EMT), which could indicate that in skin, M. leprae could be de-differentiating, directly or indirectly, other cell types into a progenitor/stem-like phenotype, facilitating mycobacterial survival and migration within the host. Alternatively, this could highlight which pathways are activated during granuloma formation and/or skin barrier assembly/disassembly.
2021-10-01 | E-MTAB-10318 | biostudies-arrayexpress
Project description:Copy number variations (CNVs) have been demonstrated as crucial substrates for evolution, adaptation and breed formation. Chinese indigenous cattle breeds exhibit a broad geographical distribution and diverse environmental adaptability. Here, we analyzed the population structure and adaptation to high altitude of Chinese indigenous cattle based on genome-wide CNVs derived from the high-density BovineHD SNP array. We successfully detected the genome-wide CNVs of 318 individuals from 24 Chinese indigenous cattle breeds and 37 yaks as outgroups. A total of 5,818 autosomal CNV regions (683 bp - 4,477,860 bp in size), covering ~14.34% of the bovine genome (UMD3.1), were identified, showing abundant CNV resources. Neighbor-joining clustering, principal component analysis (PCA), and population admixture analysis based on these CNVs support that most Chinese cattle breeds are hybrids of Bos taurus taurus (hereinafter to be referred as Bos taurus) and Bos taurus indicus (Bos indicus). The distribution patterns of the CNVs could to some extent be related to the geographical backgrounds of the habitat of the breeds, and admixture among cattle breeds from different districts. We analyzed the selective signatures of CNVs positively involved in high-altitude adaptation using pairwise Fst analysis within breeds with a strong Bos taurus background (taurine-type breeds) and within Bos taurus×Bos indicus hybrids, respectively. CNV-overlapping genes with strong selection signatures (at top 0.5% of Fst value), including LETM1 (Fst = 0.490), TXNRD2 (Fst=0.440) and STUB1 (Fst=0.420) within taurine-type breeds, and NOXA1 (Fst = 0.233), RUVBL1 (Fst=0.222) and SLC4A3 (Fst=0.154) within hybrids, were potentially involved in the adaptation to hypoxia. Thus, we provide a new profile of population structure from the CNV aspects of Chinese indigenous cattle and new insights into high-altitude adaptation in cattle.
2020-02-21 | GSE142218 | GEO