Genome-wide association study of Buruli ulcer in rural Benin

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 of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway

Communications Biology ◽

10.1038/s42003-020-0920-6 ◽

2020 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Jeremy Manry ◽

Quentin B. Vincent ◽

Christian Johnson ◽

Maya Chrabieh ◽

Lazaro Lorenzo ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Buruli Ulcer ◽

Genome Wide Association ◽

Genome Wide ◽

Autophagy Pathway

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Genome wide association study of HTLV-1–associated myelopathy/tropical spastic paraparesis in the Japanese population

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2004199118 ◽

2021 ◽

Vol 118 (11) ◽

pp. e2004199118

Author(s):

Marina Penova ◽

Shuji Kawaguchi ◽

Jun-ichirou Yasunaga ◽

Takahisa Kawaguchi ◽

Tomoo Sato ◽

...

Keyword(s):

Amino Acid ◽

Association Study ◽

Proviral Load ◽

Odds Ratio ◽

Japanese Population ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome ◽

Increased Risk

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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Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia

Scientific Reports ◽

10.1038/s41598-017-18214-z ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 8

Author(s):

Yi Han ◽

Rajkumar Dorajoo ◽

Xuling Chang ◽

Ling Wang ◽

Chiea-Chuen Khor ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Southeast Asia ◽

Association Study ◽

Genome Wide Association Study ◽

Missense Variant ◽

Genome Wide Association ◽

Genome Wide ◽

Artery Disease

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A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2016.02.014 ◽

2016 ◽

Vol 98 (4) ◽

pp. 744-754 ◽

Cited By ~ 74

Author(s):

Elizabeth J. Leslie ◽

Huan Liu ◽

Jenna C. Carlson ◽

John R. Shaffer ◽

Eleanor Feingold ◽

...

Keyword(s):

Cleft Palate ◽

Association Study ◽

Genome Wide Association Study ◽

Missense Variant ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome

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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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Family-based genome-wide association study of leprosy in Vietnam

10.1101/2020.01.30.20018432 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chaima Gzara ◽

Monica Dallmann-Sauer ◽

Marianna Orlova ◽

Nguyen Van Thuc ◽

Vu Hong Thai ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Control Sample ◽

Hla Class I ◽

Missense Variant ◽

Ethnic Origin ◽

Case Control ◽

Genome Wide Association ◽

Genome Wide ◽

Family Based

AbstractLeprosy is a chronic infectious disease of the skin and peripheral nerves with a strong genetic predisposition. Recent genome-wide approaches have identified numerous common variants associated with leprosy, almost all in the Chinese population. We conducted the first family-based genome-wide association study of leprosy in 622 affected offspring from Vietnam, followed by replication in an independent sample of 1189 leprosy cases and 671 controls of the same ethnic origin. The most significant results were observed within the HLA region, in which six SNPs displayed genome-wide significant associations, all of which were replicated in the independent case/control sample. We investigated the signal in the HLA region in more detail, by conducting a multivariate analysis on the case/control sample of 319 GWAS-suggestive HLA hits for which evidence for replication was obtained. We identified three independently associated SNPs, two located in the HLA class I region (rs1265048: OR=0.69 [0.58-0.80], combined p-value = 5.53×10−11; and rs114598080: OR=1.47 [1.46-1.48], combined p-value = 8.77×10−13), and one located in the HLA class II region (rs3187964 (OR=1.67 [1.55-1.80], combined p-value = 8.35×10−16). We also validated two previously identified risk factors for leprosy: the missense variant rs3764147 in the LACC1 gene (OR=1.52 [1.41-1.63], combined p-value = 5.06×10−14), and the intergenic variant rs6871626 located close to the IL12B gene (OR=0.73 [0.61-0.84], combined p-value = 6.44×10−8). These results shed new light on the genetic control of leprosy, by dissecting the influence of HLA SNPs, and validating the independent role of two additional variants in a large Vietnamese sample.

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