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

Author

Michelle M. Stein, Mitch Conery, Kevin M. Magnaye, Selene M. Clay, Christine Billstrand, Raluca Nicolae, Katherine Naughton, Carole Ober, and Emma E. Thompson

Subjects
Medicine, Science
Abstract

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.

Published
2021
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2. Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes

Author

Selene M. Clay, Mitch Conery, Michelle M. Stein, Carole Ober, Raluca Nicolae, Christine Billstrand, Katherine A. Naughton, Kevin M. Magnaye, and Emma E. Thompson

Subjects
Adult, Lipopolysaccharides, Male, X-Chromosome Genes, Lipopolysaccharide, Adolescent, Transcription, Genetic, Science, Genes, MHC Class II, Quantitative Trait Loci, Genes, MHC Class I, Stimulation, Human leukocyte antigen, Biology, Article, chemistry.chemical_compound, Young Adult, Genes, X-Linked, Ethnicity, Leukocytes, Humans, Child, Gene, Aged, Aged, 80 and over, Sex Characteristics, Multidisciplinary, Innate immune system, Gene Expression Profiling, Middle Aged, Peripheral blood, Immunity, Innate, Gene regulation, chemistry, Expression quantitative trait loci, Immunology, Medicine, Female, Gene expression
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.

Published
2021

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