Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups

Abstract Podoconiosis, a debilitating lymphoedema of the leg, results from barefoot exposure to volcanic clay soil in genetically susceptible individuals. A previous genome-wide association study (GWAS) conducted in the Wolaita ethnic group from Ethiopia showed association between single nucleotide...

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Autores principales:	Tewodros Gebresilase, Chris Finan, Daniel Suveges, Tesfaye Sisay Tessema, Abraham Aseffa, Gail Davey, Konstantinos Hatzikotoulas, Eleftheria Zeggini, Melanie J. Newport, Fasil Tekola-Ayele
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62fdc6fa44c241f094368907be57e630
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spelling	oai:doaj.org-article:62fdc6fa44c241f094368907be57e6302021-12-02T13:30:10ZReplication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups10.1038/s41598-021-81836-x2045-2322https://doaj.org/article/62fdc6fa44c241f094368907be57e6302021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81836-xhttps://doaj.org/toc/2045-2322Abstract Podoconiosis, a debilitating lymphoedema of the leg, results from barefoot exposure to volcanic clay soil in genetically susceptible individuals. A previous genome-wide association study (GWAS) conducted in the Wolaita ethnic group from Ethiopia showed association between single nucleotide polymorphisms (SNPs) in the HLA class II region and podoconiosis. We aimed to conduct a second GWAS in a new sample (N = 1892) collected from the Wolaita and two other Ethiopian populations, the Amhara and the Oromo, also affected by podoconiosis. Fourteen SNPs in the HLA class II region showed significant genome-wide association (P < 5.0 × 10−8) with podoconiosis. The lead SNP was rs9270911 (P = 5.51 × 10−10; OR 1.53; 95% CI 1.34–1.74), located near HLA-DRB1. Inclusion of data from the first GWAS (combined N = 2289) identified 47 SNPs in the class II HLA region that were significantly associated with podoconiosis (lead SNP also rs9270911 (P = 2.25 × 10−12). No new loci outside of the HLA class II region were identified in this more highly-powered second GWAS. Our findings confirm the HLA class II association with podoconiosis suggesting HLA-mediated abnormal induction and regulation of immune responses may have a direct role in its pathogenesis.Tewodros GebresilaseChris FinanDaniel SuvegesTesfaye Sisay TessemaAbraham AseffaGail DaveyKonstantinos HatzikotoulasEleftheria ZegginiMelanie J. NewportFasil Tekola-AyeleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tewodros Gebresilase Chris Finan Daniel Suveges Tesfaye Sisay Tessema Abraham Aseffa Gail Davey Konstantinos Hatzikotoulas Eleftheria Zeggini Melanie J. Newport Fasil Tekola-Ayele Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
description	Abstract Podoconiosis, a debilitating lymphoedema of the leg, results from barefoot exposure to volcanic clay soil in genetically susceptible individuals. A previous genome-wide association study (GWAS) conducted in the Wolaita ethnic group from Ethiopia showed association between single nucleotide polymorphisms (SNPs) in the HLA class II region and podoconiosis. We aimed to conduct a second GWAS in a new sample (N = 1892) collected from the Wolaita and two other Ethiopian populations, the Amhara and the Oromo, also affected by podoconiosis. Fourteen SNPs in the HLA class II region showed significant genome-wide association (P < 5.0 × 10−8) with podoconiosis. The lead SNP was rs9270911 (P = 5.51 × 10−10; OR 1.53; 95% CI 1.34–1.74), located near HLA-DRB1. Inclusion of data from the first GWAS (combined N = 2289) identified 47 SNPs in the class II HLA region that were significantly associated with podoconiosis (lead SNP also rs9270911 (P = 2.25 × 10−12). No new loci outside of the HLA class II region were identified in this more highly-powered second GWAS. Our findings confirm the HLA class II association with podoconiosis suggesting HLA-mediated abnormal induction and regulation of immune responses may have a direct role in its pathogenesis.
format	article
author	Tewodros Gebresilase Chris Finan Daniel Suveges Tesfaye Sisay Tessema Abraham Aseffa Gail Davey Konstantinos Hatzikotoulas Eleftheria Zeggini Melanie J. Newport Fasil Tekola-Ayele
author_facet	Tewodros Gebresilase Chris Finan Daniel Suveges Tesfaye Sisay Tessema Abraham Aseffa Gail Davey Konstantinos Hatzikotoulas Eleftheria Zeggini Melanie J. Newport Fasil Tekola-Ayele
author_sort	Tewodros Gebresilase
title	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
title_short	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
title_full	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
title_fullStr	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
title_full_unstemmed	Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
title_sort	replication of hla class ii locus association with susceptibility to podoconiosis in three ethiopian ethnic groups
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/62fdc6fa44c241f094368907be57e630
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Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups

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