Abstract
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.
Highlights
Differences in both disease severity, prevalence, symptoms, and age of onset vary greatly between males and females (Morrow, 2015)
Using the Gene Expression Omnibus (GEO; Barrett et al, 2013) and ArrayExpress (Brazma et al, 2003) we identified 22 microarray data sets containing a total of 2502 samples, in 15 different human tissues (Table 1)
Despite the frontal lobe of the cerebral cortex or frontal cortex (FC) and cerebellum (CB) data sets containing the greatest number of samples, with 455 and 553 samples, respectively, we detected only a small number of sex-biased genes compared to other tissues such as the anterior cingulate cortex (AnCg) and the heart which contained the greatest number of sex-biased genes with average sample sizes (Figure 1, Table 2)
Summary
Differences in both disease severity, prevalence, symptoms, and age of onset vary greatly between males and females (Morrow, 2015). Sex differences have been identified in the age of onset of brain diseases such as schizophrenia, where males develop symptoms between 18 and 25 years of age whereas females develop symptoms between 25 and 35 years (Ochoa et al, 2012). Reported atonic seizures in epilepsy are more frequent in males compared to females (6.5 vs 1.7%; Carlson et al, 2014). These sex differences in diseases may be the result of tissuespecific differential gene expression between males and females. Gene expression may have a role in orchestrating sex differences in the prevalence of diseases
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