Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms
Abstract Background Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs fo...
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doaj-5e8e3905f3b34694bad12edbc81f499c2020-11-24T21:48:38ZengBMCBiology of Sex Differences2042-64102017-10-018111210.1186/s13293-017-0153-7Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphismsMagdalena Lindén0Jorge I. Ramírez Sepúlveda1Tojo James2Gudny Ella Thorlacius3Susanna Brauner4David Gómez-Cabrero5Tomas Olsson6Ingrid Kockum7Marie Wahren-Herlenius8Unit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska InstitutetUnit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska InstitutetUnit of Neuroimmunology, Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska InstitutetUnit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska InstitutetUnit of Neuroimmunology, Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska InstitutetUnit of Computational Medicine, Karolinska University Hospital, Karolinska InstitutetUnit of Neuroimmunology, Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska InstitutetUnit of Neuroimmunology, Department of Clinical Neuroscience, Karolinska University Hospital, Karolinska InstitutetUnit of Experimental Rheumatology, Department of Medicine, Karolinska University Hospital, Karolinska InstitutetAbstract Background Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. Methods We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. Results We found ten SNPs affecting the expression of 16 different genes (FDR < 0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). Conclusions We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases.http://link.springer.com/article/10.1186/s13293-017-0153-7Sjögren’s syndromeSLEAutoimmunitySex differenceeQTL |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magdalena Lindén Jorge I. Ramírez Sepúlveda Tojo James Gudny Ella Thorlacius Susanna Brauner David Gómez-Cabrero Tomas Olsson Ingrid Kockum Marie Wahren-Herlenius |
spellingShingle |
Magdalena Lindén Jorge I. Ramírez Sepúlveda Tojo James Gudny Ella Thorlacius Susanna Brauner David Gómez-Cabrero Tomas Olsson Ingrid Kockum Marie Wahren-Herlenius Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms Biology of Sex Differences Sjögren’s syndrome SLE Autoimmunity Sex difference eQTL |
author_facet |
Magdalena Lindén Jorge I. Ramírez Sepúlveda Tojo James Gudny Ella Thorlacius Susanna Brauner David Gómez-Cabrero Tomas Olsson Ingrid Kockum Marie Wahren-Herlenius |
author_sort |
Magdalena Lindén |
title |
Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms |
title_short |
Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms |
title_full |
Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms |
title_fullStr |
Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms |
title_full_unstemmed |
Sex influences eQTL effects of SLE and Sjögren’s syndrome-associated genetic polymorphisms |
title_sort |
sex influences eqtl effects of sle and sjögren’s syndrome-associated genetic polymorphisms |
publisher |
BMC |
series |
Biology of Sex Differences |
issn |
2042-6410 |
publishDate |
2017-10-01 |
description |
Abstract Background Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B cells, and notably high female-to-male incidence ratios. Genome-wide association studies have identified several susceptibility SNPs for both diseases. Many SNPs in the genome are expression quantitative trait loci (eQTLs), with context-dependent effects. Assuming that sex is a biological context, we investigated whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach to understand if they display sex-specific effects. Methods We used genome-wide genotype and gene expression data from primary B cells from 125 males and 162 females. The MatrixEQTL R package was used to identify eQTLs within a genomic window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex interaction term. Results We found ten SNPs affecting the expression of 16 different genes (FDR < 0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D, rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune compartment and B cells. By analyzing the SNP * sex interaction terms, we identified six genes with differentially regulated expression in females compared to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1 locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus), and DHX9 (NCF2 locus). Conclusions We identified several unknown sex-specific eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel insight into how gene-sex interactions may contribute to the sex bias in systemic autoimmune diseases. |
topic |
Sjögren’s syndrome SLE Autoimmunity Sex difference eQTL |
url |
http://link.springer.com/article/10.1186/s13293-017-0153-7 |
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