Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes

Abstract Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated...

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Autores principales:	Michelle M. Stein, Mitch Conery, Kevin M. Magnaye, Selene M. Clay, Christine Billstrand, Raluca Nicolae, Katherine Naughton, Carole Ober, Emma E. Thompson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba1b370061be4fbe9a9e6a4402d39e72
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spelling	oai:doaj.org-article:ba1b370061be4fbe9a9e6a4402d39e722021-12-02T14:01:32ZSex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes10.1038/s41598-020-80145-z2045-2322https://doaj.org/article/ba1b370061be4fbe9a9e6a4402d39e722021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80145-zhttps://doaj.org/toc/2045-2322Abstract Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated sex-specific transcriptional responses of peripheral blood leukocytes (PBLs) to innate immune stimulation by lipopolysaccharide (LPS) in 46 male and 66 female members of the Hutterite community, who practice a communal lifestyle. We identified 1217 autosomal and 54 X-linked genes with sex-specific responses to LPS, as well as 71 autosomal and one X-linked sex-specific expression quantitative trait loci (eQTLs). Despite a similar proportion of the 15 HLA genes responding to LPS compared to all expressed autosomal genes, there was a significant over-representation of genes with sex by treatment interactions among HLA genes. We also observed an enrichment of sex-specific differentially expressed genes in response to LPS for X-linked genes compared to autosomal genes, suggesting that HLA and X-linked genes may disproportionately contribute to sex disparities in risk for immune-mediated diseases.Michelle M. SteinMitch ConeryKevin M. MagnayeSelene M. ClayChristine BillstrandRaluca NicolaeKatherine NaughtonCarole OberEmma E. ThompsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michelle M. Stein Mitch Conery Kevin M. Magnaye Selene M. Clay Christine Billstrand Raluca Nicolae Katherine Naughton Carole Ober Emma E. Thompson Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
description	Abstract Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated sex-specific transcriptional responses of peripheral blood leukocytes (PBLs) to innate immune stimulation by lipopolysaccharide (LPS) in 46 male and 66 female members of the Hutterite community, who practice a communal lifestyle. We identified 1217 autosomal and 54 X-linked genes with sex-specific responses to LPS, as well as 71 autosomal and one X-linked sex-specific expression quantitative trait loci (eQTLs). Despite a similar proportion of the 15 HLA genes responding to LPS compared to all expressed autosomal genes, there was a significant over-representation of genes with sex by treatment interactions among HLA genes. We also observed an enrichment of sex-specific differentially expressed genes in response to LPS for X-linked genes compared to autosomal genes, suggesting that HLA and X-linked genes may disproportionately contribute to sex disparities in risk for immune-mediated diseases.
format	article
author	Michelle M. Stein Mitch Conery Kevin M. Magnaye Selene M. Clay Christine Billstrand Raluca Nicolae Katherine Naughton Carole Ober Emma E. Thompson
author_facet	Michelle M. Stein Mitch Conery Kevin M. Magnaye Selene M. Clay Christine Billstrand Raluca Nicolae Katherine Naughton Carole Ober Emma E. Thompson
author_sort	Michelle M. Stein
title	Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
title_short	Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
title_full	Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
title_fullStr	Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
title_full_unstemmed	Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes
title_sort	sex-specific differences in peripheral blood leukocyte transcriptional response to lps are enriched for hla region and x chromosome genes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ba1b370061be4fbe9a9e6a4402d39e72
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Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes

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