Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans
Open accessAbstract
The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.
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Sex/gender differences exist in the nature of symptoms, age of onset, frequency of episode recurrence, chronicity, comorbidities, precursors, triggers, functional impairment, and treatment response.
“Whereas, most research on sex/gender differences in mental disorders has focused on prevalence and symptom severity, there also exist differences in the nature of symptoms, in age of onset, in frequency of episode recurrence, in chronicity, comorbidities, precursors, triggers, functional impairment, and treatment response (24, 25).”
From Where Sex Meets Gender: How Sex and Gender Come Together to Cause Sex Differences in Mental Illness (2022) · cites this paper as [24]
The Introduction (no page number in our copy) reports sex differences in symptoms and age of onset, including a schizophrenia example. It does not address episode recurrence, chronicity, comorbidities, precursors, triggers, functional impairment, or treatment response in mental disorders. (LLM, conf=0.87)
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Grumelot, S., Mannering, F. L., Campbell, N., Ashokkumar, M. S., Howard, E., Serpooshan, V., Asgari, M., Latifi, N., Vali, H., Aguirre, A., et al. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.172977 · Cited by 2 · see citing works
Schneider, A. L., Martins-Silva, R., Kaizeler, A., Saraiva-Agostinho, N., & Barbosa‐Morais, N. L. (2024) · eLife · doi:10.7554/elife.88623.3 · Cited by 2 · see citing works
Ghione, C. R., & Dean, M. D. (2025) · Genome Biology and Evolution · doi:10.1093/gbe/evaf068 · Cited by 2 · see citing works
Benjamin, K. J., Arora, R., Stolz, J. M., D’Ignazio, L., Collado‐Torres, L., Hyde, T. M., Kleinman, J. E., Weinberger, D. R., Paquola, A. C. M., & Erwin, J. A. (2022) · medRxiv · doi:10.1101/2022.09.30.22280452 · Cited by 2 · see citing works
The influence of Sex on microRNA expression in Human Skeletal MusclePreprint
Hiam, D., Landen, S., Jacques, M., Voisin, S. A. C., Lamon, S., & Eynon, N. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.27.530361 · Cited by 2 · see citing works
Evolution of sex-biased gene expression during transitions to separate sexes in the Silene genusPreprint
Prentout, D., Muyle, A., Zemp, N., Filali, A. E., Boussau, B., Touzet, P., Widmer, A., Käfer, J., & Marais, G. A. B. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.02.560480 · Cited by 2 · see citing works
Huang, Y., Kurniansyah, N., Levey, D. F., Gelernter, J. E., Huffman, J. E., Cho, K., Wilson, P. W. F., Gottlieb, D. J., Rice, K. M., & Sofer, T. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.07.015 · Cited by 1 · see citing works
Evolution of Sex-Biased Gene Expression During Transitions to Separate Sexes in the Silene Genus
Prentout, D., Muyle, A., Zemp, N., Filali, A. E., Boussau, B., Touzet, P., Käfer, J., & Marais, G. A. B. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf229 · Cited by 1 · see citing works
How Does Biological Sex Impact Mucosal Bacterial Infection? Mucosal Defenses and Bacterial Detection
Finn, L. R., & Ingersoll, M. A. (2026) · Immunological Reviews · doi:10.1111/imr.70112 · Cited by 2 · see citing works
- Authors
- Mayne, B. T., Bianco-Miotto, T., Buckberry, S., Breen, J., Clifton, V., Shoubridge, C., & Roberts, C. T.
- Affiliations
- The University of Adelaide (AU)
- The University of Western Australia (AU)
- The University of Queensland (AU)
- Corresponding author
- Roberts, Claire T.
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2016-10-13
- Volume
- 7
- Pages
- 183-183
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC5062749
- OpenAlex
- W2529891619
- Cited by
- 140
- References
- 93
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 14 · 2023: 28 · 2022: 17 · 2021: 17 · 2020: 13 · 2019: 9 · 2018: 11 · 2017: 5 · 2016: 1
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- NOVA (University of Newcastle Australia) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (GNT1059120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- sex-biased gene expression, sexually dimorphic traits, human tissue, brain, anterior cingulate cortex, sex chromosomes, androgen response element, estrogen response element, sex differences in disease
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