A wavelet-based Monte Carlo simulation of Odds Ratio Contour in genome-wide association study

HTLV-1–associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10−9) and class II (P = 1.21 × 10−8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10−5), HLA-B*07:02 (P = 4.97 × 10−10), HLA-DRB1*01:01 (P = 1.15 × 10−9) and HLA-DQB1*05:01 (P = 2.30 × 10−9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10−5), HLA-DRB1*15:01 (P = 1.06 × 10−5) and HLA-DQB1*06:02 (P = 1.78 × 10−6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10−10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

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PARALLEL MULTI-PROPOSAL AND MULTI-CHAIN MCMC FOR CALCULATING P-VALUE OF GENOME-WIDE ASSOCIATION STUDY

Parallel Processing Letters ◽

10.1142/s0129626413500084 ◽

2013 ◽

Vol 23 (03) ◽

pp. 1350008 ◽

Cited By ~ 1

Author(s):

DI ZHAO ◽

SHENGHUA NI

Keyword(s):

Monte Carlo ◽

Association Study ◽

High Performance ◽

Genome Wide Association Study ◽

Convergence Condition ◽

Genome Wide Association ◽

P Value ◽

The Novel ◽

Genome Wide ◽

Multiple Chain

In this paper, by the novel idea of integrating multiple-proposal algorithm and multiple-chain algorithm by parallel computing, we develop a highly efficient sampler for approximating statistical distributions: parallel Multi-proposal and Multi-chain Markov Chain Monte Carlo (pMPMC3), and we illustrate the high performance of this sampler by calculating P-value (odds ratio significance) for Genome Wide Association Study (GWAS). Computational results show that, by setting the convergence condition as the standard deviation of P-value is less than 10−3, pMPMC3 with 4 proposals and 4 chains obtains a convergent P-value within 106 iterations, while the conventional method Monte Carlo simulation does not obtain convergent P-values even in 107 iterations. We also test pMPMC3 by changing the number of chains, the number of proposals and the size of the dataset on a cluster with maximum 600 processes, the algorithm scales well.

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Genome-wide association study of Buruli ulcer in rural Benin

10.1101/19012096 ◽

2019 ◽

Author(s):

Jeremy Manry ◽

Quentin B. Vincent ◽

Maya Chrabieh ◽

Lazaro Lorenzo ◽

Ioannis Theodorou ◽

...

Keyword(s):

Association Study ◽

Odds Ratio ◽

Genome Wide Association Study ◽

Buruli Ulcer ◽

Missense Variant ◽

Skin Lesions ◽

Mycobacterium Ulcerans ◽

Genome Wide Association ◽

Genome Wide ◽

Autophagy Pathway

AbstractBuruli ulcer, caused by Mycobacterium ulcerans, is the third mycobacterial disease worldwide characterized by devastating necrotizing skin lesions. The role of host genetics in susceptibility to Buruli ulcer has long been suggested. We conduct the first genome-wide association study of Buruli ulcer on a combined sample of 1,524 well characterized patients and controls from rural Benin. Two-stage analyses identify two novel associated loci located within lincRNA genes: rs9814705 in ENSG00000240095.1 (P = 2.85×10−7; odds ratio = 1.80 [1.43-2.27]), and rs76647377 in LINC01622 (P = 9.85×10−8; hazard ratio = 0.41 [0.28-0.60]). Furthermore, we replicate the protective effect of allele G of a missense variant located in ATG16L1, and previously shown to decrease bacterial autophagy (rs2241880, P = 0.003; odds ratio = 0.31 [0.14-0.68]). Our results suggest lincRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.

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Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease

European Respiratory Journal ◽

10.1183/13993003.02269-2019 ◽

2021 ◽

pp. 1902269

Author(s):

Ho Namkoong ◽

Yosuke Omae ◽

Takanori Asakura ◽

Makoto Ishii ◽

Shoji Suzuki ◽

...

Keyword(s):

Association Study ◽

Mycobacterium Avium ◽

Odds Ratio ◽

Complex Disease ◽

Genome Wide Association Study ◽

Host Susceptibility ◽

Genome Wide Association ◽

European Ancestry ◽

Nucleotide Polymorphisms ◽

Genome Wide

RationaleNontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.ObjectivesWe aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen.MethodsThis genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.ResultsThe GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64E−13, odds ratio=0.54), which is in an intronic region of the calcineurin like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. This SNP was also significantly associated with the disease in patients of Korean (p=2.18E−12, odds ratio=0.54) and European (p=5.12E−03, odds ratio=0.63) ancestry.ConclusionsWe identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.

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