Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans

Abstract Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American ca...

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Autores principales:	Nathan Nakatsuka, Nick Patterson, Nikolaos A. Patsopoulos, Nicolas Altemose, Arti Tandon, Ashley H. Beecham, Jacob L. McCauley, Noriko Isobe, Stephen Hauser, Philip L. De Jager, David A. Hafler, Jorge R. Oksenberg, David Reich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bbacc879fe7649be855764f1db11ac9a
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spelling	oai:doaj.org-article:bbacc879fe7649be855764f1db11ac9a2021-12-02T18:36:14ZTwo genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans10.1038/s41598-020-74035-72045-2322https://doaj.org/article/bbacc879fe7649be855764f1db11ac9a2020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-74035-7https://doaj.org/toc/2045-2322Abstract Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.Nathan NakatsukaNick PattersonNikolaos A. PatsopoulosNicolas AltemoseArti TandonAshley H. BeechamJacob L. McCauleyNoriko IsobeStephen HauserPhilip L. De JagerDavid A. HaflerJorge R. OksenbergDavid ReichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathan Nakatsuka Nick Patterson Nikolaos A. Patsopoulos Nicolas Altemose Arti Tandon Ashley H. Beecham Jacob L. McCauley Noriko Isobe Stephen Hauser Philip L. De Jager David A. Hafler Jorge R. Oksenberg David Reich Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
description	Abstract Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.
format	article
author	Nathan Nakatsuka Nick Patterson Nikolaos A. Patsopoulos Nicolas Altemose Arti Tandon Ashley H. Beecham Jacob L. McCauley Noriko Isobe Stephen Hauser Philip L. De Jager David A. Hafler Jorge R. Oksenberg David Reich
author_facet	Nathan Nakatsuka Nick Patterson Nikolaos A. Patsopoulos Nicolas Altemose Arti Tandon Ashley H. Beecham Jacob L. McCauley Noriko Isobe Stephen Hauser Philip L. De Jager David A. Hafler Jorge R. Oksenberg David Reich
author_sort	Nathan Nakatsuka
title	Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
title_short	Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
title_full	Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
title_fullStr	Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
title_full_unstemmed	Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans
title_sort	two genetic variants explain the association of european ancestry with multiple sclerosis risk in african-americans
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/bbacc879fe7649be855764f1db11ac9a
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Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans

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