Sex differences in the human peripheral blood transcriptome

BackgroundGenomes of men and women differ in only a limited number of genes located on the sex chromosomes, whereas the transcriptome is far more sex-specific. Identification of sex-biased gene expression will contribute to understanding the molecular basis of sex-differences in complex traits and common diseases.ResultsSex differences in the human peripheral blood transcriptome were characterized using microarrays in 5,241 subjects, accounting for menopause status and hormonal contraceptive use. Sex-specific expression was observed for 582 autosomal genes, of which 57.7% was upregulated in women (female-biased genes). Female-biased genes were enriched for several immune system GO categories, genes linked to rheumatoid arthritis (16%) and genes regulated by estrogen (18%). Male-biased genes were enriched for genes linked to renal cancer (9%). Sex-differences in gene expression were smaller in postmenopausal women, larger in women using hormonal contraceptives and not caused by sex-specific eQTLs, confirming the role of estrogen in regulating sex-biased genes.ConclusionsThis study indicates that sex-bias in gene expression is extensive and may underlie sex-differences in the prevalence of common diseases.

• Publication year

  2014

• Venue

  BMC Genomics

• Publication date

  2014-01-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1471-2164-15-33PMID 24438232PMCID 3904696
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Sex differences in the human peripheral blood transcriptome

  2014cited by this paper
• The evolutionary causes and consequences of sex-biased gene expression

  2013cited by this paper
• Genome-Wide Analysis of Chromatin States Reveals Distinct Mechanisms of Sex-Dependent Gene Regulation in Male and Female Mouse Liver

  2013cited by this paper
• Population structure, migration, and diversifying selection in the Netherlands

  2013cited by this paper
• Lipocalin 2 in cancer: when good immunity goes bad.

  2012cited by this paper
• Sex-Specific Modulation of Gene Expression Networks in Murine Hypothalamus

  2012cited by this paper
• Sex-biased genetic effects on gene regulation in humans

  2012cited by this paper
• Emotion regulation and psychopathology: the role of gender.

  2012cited by this paper
• Mid-Regional Pro-Adrenomedullin in Acute Heart Failure: A Better Biomarker or Just Another Biomarker?

  2012cited by this paper
• Autocrine CSF-1 and CSF-1 receptor coexpression promotes renal cell carcinoma growth.

  2012cited by this paper
• Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression

  2012cited by this paper
• The Evolution of Antiplatelet Therapy in the Treatment of Acute Coronary Syndromes

  2012cited by this paper
• Genome-wide meta-analysis of common variant differences between men and women

  2012cited by this paper
• Horizontal transfer of RNAs: exosomes as mediators of intercellular communication

  2012cited by this paper
• The influence of sex and gender on the immune response.

  2012cited by this paper
• Sex Differences in Genetic Architecture of Complex Phenotypes?

  2012cited by this paper
• Matrix eQTL: ultra fast eQTL analysis via large matrix operations

  2011cited by this paper
• Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease

  2011influential reference
• Strategies for aggregating gene expression data: The collapseRows R function

  2011cited by this paper
• Lactoferrin and cancer in different cancer models.

  2011cited by this paper
• Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell cytotoxicity.

  2011cited by this paper
• Dynamic, Sex-Differential STAT5 and BCL6 Binding to Sex-Biased, Growth Hormone-Regulated Genes in Adult Mouse Liver

  2011cited by this paper
• Gene Duplication and the Genome Distribution of Sex-Biased Genes

  2011cited by this paper
• A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells.

  2011cited by this paper
• The G-protein-coupled estrogen receptor GPER in health and disease

  2011cited by this paper
• The Demoiselle of X-Inactivation: 50 Years Old and As Trendy and Mesmerising As Ever

  2011cited by this paper
• Sex differences in epigenetic mechanisms may underlie risk and resilience for mental health disorders

  2011cited by this paper
• Sex bias in trials and treatment must end

  2010cited by this paper
• Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression

  2010cited by this paper
• Sex-specific gene expression in the BXD mouse liver.

  2010cited by this paper
• The Netherlands Twin Register Biobank: A Resource for Genetic Epidemiological Studies

  2010cited by this paper
• Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors

  2010cited by this paper
• Lactoferrin: the path from protein to gene

  2010cited by this paper
• Perforin deficiency and susceptibility to cancer

  2010cited by this paper
• Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography.

  2010cited by this paper
• The evolving role of oestrogens and their receptors in the development and progression of prostate cancer.

  2009cited by this paper
• Why are women predisposed to autoimmune rheumatic diseases?

  2009cited by this paper
• ChIP‐Seq of ERα and RNA polymerase II defines genes differentially responding to ligands

  2009cited by this paper
• Effect of menopause on gene expression pattern in bone tissue of nonosteoporotic women

  2009cited by this paper
• The unique genomic properties of sex-biased genes: Insights from avian microarray data

  2008cited by this paper
• WGCNA: an R package for weighted correlation network analysis

  2008cited by this paper
• An Evolutionarily Conserved Sexual Signature in the Primate Brain

  2008cited by this paper
• Rapid recruitment of temporally distinct vascular gene sets by estrogen.

  2008cited by this paper
• Sex differences in renal cell cancer presentation and survival: an analysis of the National Cancer Database, 1993-2004.

  2008cited by this paper
• Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects

  2008cited by this paper
• Sex-Related Differences in Gene Expression in Human Skeletal Muscle

  2008cited by this paper
• Sex-specific genetic architecture of human disease

  2008cited by this paper
• The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods

  2008influential reference
• Human PAML browser: a database of positive selection on human genes using phylogenetic methods

  2007cited by this paper
• Effect of menopause on gene expression profiles of circulating monocytes: a pilot in vivo microarray study.

  2007cited by this paper
• Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.

  2007cited by this paper
• Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status

  2007cited by this paper
• The evolution of sex-biased genes and sex-biased gene expression

  2007cited by this paper
• Constraint and turnover in sex-biased gene expression in the genus Drosophila

  2007cited by this paper
• Why men's hearts break: cardiovascular effects of sex steroids.

  2007cited by this paper
• Gender-specific differences in expression in human lymphoblastoid cell lines

  2007cited by this paper
• Genome-wide analysis of estrogen receptor binding sites

  2006cited by this paper
• The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor.

  2006cited by this paper
• Interleukin-6 in rheumatoid arthritis

  2006cited by this paper
• Modulation of growth hormone action by sex steroids

  2006cited by this paper
• Tissue-specific expression and regulation of sexually dimorphic genes in mice.

  2006cited by this paper
• Netherlands Twin Register: From Twins to Twin Families

  2006cited by this paper
• BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks

  2005cited by this paper
• Initial sequence of the chimpanzee genome and comparison with the human genome

  2005cited by this paper
• A General Framework for Weighted Gene Co-Expression Network Analysis

  2005cited by this paper
• X-inactivation profile reveals extensive variability in X-linked gene expression in females

  2005cited by this paper
• A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

  2005cited by this paper
• Profiling gene expression in whole blood samples following an in-vitro challenge.

  2004cited by this paper
• Gene regulation and DNA damage in the ageing human brain

  2004cited by this paper
• The use of linear mixed models to estimate variance components from data on twin pairs by maximum likelihood.

  2004cited by this paper
• Estrogen regulation of growth hormone action.

  2004cited by this paper
• Identification and phylogenetic analysis of Dictyostelium discoideum kinesin proteins

  2003cited by this paper
• Sex-Dependent Gene Expression and Evolution of the Drosophila Transcriptome

  2003cited by this paper
• Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

  2002cited by this paper
• Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

  2002cited by this paper
• Progesterone receptors – animal models and cell signaling in breast cancer: The role of oestrogen and progesterone receptors in human mammary development and tumorigenesis

  2002cited by this paper
• Sex differences in autoimmune disease

  2001cited by this paper
• Gene Ontology: tool for the unification of biology

  2000cited by this paper
• The latent transforming growth factor binding protein (LTBP) family

  2000cited by this paper
• The latent transforming growth factor beta binding protein (LTBP) family.

  2000cited by this paper
• Functional coherence of the human Y chromosome.

  1997cited by this paper
• Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

  1985cited by this paper
• Edinburgh Research Explorer Genome-wide meta-analysis of common variant differences between men and women

  year unknowncited by this paper

• Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling in male mice

  2025cites this paper
• The sex-biased chromatin modifier SMC1A promotes autoimmunity by shaping inflammatory pathways in patients with SLE

  2025cites this paper
• A Estratégias para Interferir no Processo de Envelhecimento: Um Foco em Telomerase e Intervenções Biomoleculares

  2025cites this paper
• Assessing transcriptomic signatures of aging: Testing an mRNA marker panel for forensic age estimation of blood samples.

  2025cites this paper
• Molecular heterogeneity in human stroke - What can we learn from the peripheral blood transcriptome?

  2025cites this paper
• Decoding sex differences in human immunity through systems immunology

  2025influential citation
• Increased ectodysplasin-A2-receptor EDA2R is a ubiquitous hallmark of aging and mediates parainflammatory responses

  2025cites this paper
• The interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank

  2025cites this paper
• Genome-wide study of gene-by-sex interactions identifies risks for cleft palate

  2024cites this paper
• Combined transcriptomics and proteomics unveil the impact of vitamin C in modulating specific protein abundance in the mouse liver

  2024cites this paper
• Whole blood transcriptome analysis for age- and gender-specific gene expression profiling in Japanese individuals

  2024cites this paper
• Transcriptomic and Metabolomic analyses in Monozygotic and Dizygotic twins.

  2024cites this paper
• Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals

  2024cites this paper
• Genome-wide study of gene-by-sex interactions identifies risks for cleft palate

  2024cites this paper
• Sexual dimorphism in fish innate immunity: a functional and transcriptional study in yellowtail kingfish.

  2024cites this paper
• The impact of sex on HIV immunopathogenesis and therapeutic interventions

  2024cites this paper
• Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins

  2024cites this paper
• Association of Circadian Clock Gene Expression with Pediatric/Adolescent Asthma and Its Comorbidities

  2023cites this paper
• Meta-analysis of differential expression of sex-biased and common drug metabolism enzymes and transporters genes in blood transcriptomics of mental disorders

  2023cites this paper
• The Evolving Landscape of Gout in the Female: A Narrative Review

  2023cites this paper
• Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins

  2023cites this paper
• Extensive Alternative Splicing Patterns in Systemic Lupus Erythematosus Highlight Sexual Differences

  2023cites this paper
• Sex differences in neuroimmunoendocrine communication. Involvement on longevity.

  2023cites this paper
• Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins

  2023cites this paper
• Female cardiovascular biology and resilience in the setting of physiological and pathological stress

  2023cites this paper
• Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies

  2023cites this paper
• Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response.

  2022cites this paper
• The landscape of expression and alternative splicing variation across human traits

  2022cites this paper
• Blood transcriptome comparison between sexes and their function in 4-week Rhode Island red chickens

  2022cites this paper
• Alzheimer’s disease-related transcriptional sex differences in myeloid cells

  2022cites this paper
• Differentially Expressed Genes and Pathways Involved in the Development of PTSD in World Trade Center Responders

  2022cites this paper
• 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon

  2022cites this paper
• Limited evidence for blood eQTLs in human sexual dimorphism

  2022cites this paper
• The influence of age and sex in sarcoidosis

  2022cites this paper
• Serum starvation induces sexual dimorphisms in secreted proteins of human umbilical vein endothelial cells (HUVECs) from twin pairs

  2022cites this paper
• Long non-coding RNA Xist contribution in systemic lupus erythematosus and rheumatoid arthritis.

  2022cites this paper
• Sexual dimorphism of monocyte transcriptome in individuals with chronic low-grade inflammation

  2021cites this paper
• Sex disparities in influenza: A multiscale network analysis

  2021cites this paper
• Gender Variations in the Oral Microbiomes of Elderly Patients with Initial Periodontitis

  2021influential citation
• Predicting lithium treatment response in bipolar patients using gender-specific gene expression biomarkers and machine learning [version 3; peer review: 1 approved, 2 approved with reservations]

  2021cites this paper
• Single‐cell transcriptomics analysis of mild cognitive impairment in World Trade Center disaster responders

  2021cites this paper
• Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics

  2021influential citation
• Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes

  2021cites this paper
• Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation

  2021cites this paper
• Sex differences in genetic architecture in the UK Biobank

  2021cites this paper
• Sex-specific gene expression in the blood of four primates.

  2021cites this paper
• Mapping the transcriptomics landscape of post-traumatic stress disorder symptom dimensions in World Trade Center responders

  2021cites this paper
• Predicting lithium treatment response in bipolar patients using gender-specific gene expression biomarkers and machine learning [version 1; peer review: 1 approved with reservations]

  2021cites this paper
• Transcription factors in SOX Family: potent regulators for cancer initiation and development in the human body.

  2020cites this paper
• Male predominance in reported Visceral Leishmaniasis cases: Nature or nurture? A comparison of population-based with health facility-reported data

  2020cites this paper
• The impact of sex differences on genomic research.

  2020cites this paper
• Integrating biological knowledge and gene expression data using pathway-guided random forests: a benchmarking study

  2020cites this paper
• Peripheral blood gene expression signatures associated with epilepsy and its etiologic classification.

  2020cites this paper
• Transcriptomic analyses of humans and mice provide insights into depression

  2020cites this paper
• Sex Chromosomes and Sex Phenotype Contribute to Biased DNA Methylation in Mouse Liver

  2020cites this paper
• Sex-Dependent Shared and Non-Shared Genetic Architecture Across Mood and Psychotic Disorders

  2020cites this paper
• Autosomal sex-biased genetic regulation of the stress response

  2020cites this paper
• An integrative study of five biological clocks in somatic and mental health

  2020cites this paper
• No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing

  2020cites this paper
• Genetics and Epigenetics of Sex Bias: Insights from Human Cancer and Autoimmunity.

  2020cites this paper
• Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets

  2020cites this paper
• Sexual differences in genetic architecture in UK Biobank

  2020cites this paper
• Inflammation and Mitochondrial Dysfunction in Autism Spectrum Disorder.

  2020cites this paper
• Y disruption, autosomal hypomethylation and poor male lung cancer survival

  2020cites this paper
• Trypanosoma cruzi

  2020cites this paper
• Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders

  2019cites this paper
• Age estimation by measurement of open apices in tooth roots: Study using Saudi Arabian samples.

  2019cites this paper
• Sex-Related Differences in Immune Response and Symptomatic Manifestations to Infection with Leishmania Species

  2019influential citation
• Sexual dimorphism in the expression of GKN2 and FOXA2 genes in the human stomach

  2019cites this paper
• Sex Differences in Older Adults' Immune Responses to Seasonal Influenza Vaccination

  2019cites this paper
• Estrogen interacts with glucocorticoids in the regulation of lipocalin 2 expression in human adipose tissue. Reciprocal roles of estrogen receptor α and β in insulin resistance?

  2019cites this paper
• XIST and RPS4Y1 long non-coding RNA transcriptome as sex biomarkers in different body fluids

  2019cites this paper
• Paradoxical role of lipocalin-2 in metabolic disorders and neurological complications.

  2019cites this paper
• SCN11A mRNA levels in female bipolar disorder PBMCs as tentative biomarker for distinct patient sub‐phenotypes

  2019cites this paper
• ImmGen report: sexual dimorphism in the immune system transcriptome

  2019cites this paper
• A characterization of cis- and trans-heritability of RNA-Seq-based gene expression

  2019cites this paper
• The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs

  2019cites this paper
• Considering the Patient Perspective: Challenges Facing Women with Axial Spondyloarthritis and Psoriatic Arthritis

  2019cites this paper
• Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection

  2019cites this paper
• Investigating the role of sex and genetic variation in the FADS1/2 genes on lipid and fatty acid profiles and the potential impact on response to EPA and DHA supplementation

  2019cites this paper
• Distinctions between sex and time in patterns of DNA methylation across puberty

  2019cites this paper
• The Effects of Age, Cigarette Smoking, Sex, and Race on the Qualitative Characteristics of Lung Transcriptome

  2019cites this paper
• Blood Transcriptome Analysis reveals Age-associated changes in Expression Profile of Immune-Related Gene in Golden snub-nosed Monkey (Rhinopithecus roxellana)

  2019cites this paper
• Blood Transcriptome Analysis reveals Age-associated changes in 4 Expression Profile of Immune-Related Gene in Golden snub-nosed 5 Monkey( Rhinopithecus )

  2019cites this paper
• Temporal progression of gene regulation of peripheral white blood cells explains gender dimorphism of critically ill patients after trauma

  2019cites this paper
• Considering the Patient Perspective: Challenges Facing Women with Axial Spondyloarthritis and Psoriatic Arthritis

  2019cites this paper
• The role of sex in the genomics of human complex traits

  2018cites this paper
• Predicting lithium treatment response in bipolar patients using gender-specific gene expression biomarkers and machine learning

  2018cites this paper
• Epidemiological and Experimental Evidence for Sex-Dependent Differences in the Outcome of Leishmania infantum Infection.

  2018cites this paper
• X chromosome dosage and presence of SRY shape sex-specific differences in DNA methylation at an autosomal region in human cells

  2018cites this paper
• Sex differences in the late first trimester human placenta transcriptome

  2018cites this paper
• Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man

  2018cites this paper
• Sex-Based Differences in Human Immunodeficiency Virus Type 1 Reservoir Activity and Residual Immune Activation

  2018cites this paper
• The Association of Dietary Cholesterol and Fatty Acids with Dyslipidemia in Chinese Metropolitan Men and Women

  2018cites this paper
• Genetic loci associated with heart rate variability and their effects on cardiac disease risk

  2017cites this paper
• Gene expression associated with PTSD in World Trade Center responders: An RNA sequencing study

  2017cites this paper
• Interleukin-1 and estrogen protect against disseminating dentoalveolar infections

  2017cites this paper
• Using genetic methods to get insight into human complex traits

  2017cites this paper
• Investigation of immunity related genes in a disease host using applied bioinformatics

  2017cites this paper
• Age, gender and UV-exposition related effects on gene expression in in vivo aged short term cultivated human dermal fibroblasts

  2017cites this paper