title: Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans.
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.
authors: Robinson Research Institute, University of AdelaideAdelaide, SA, Australia; Adelaide Medical School, University of AdelaideAdelaide, SA, Australia.
authors: Benjamin T
authors: BT
authors: Mayne
authors: Robinson Research Institute, University of AdelaideAdelaide, SA, Australia; School of Agriculture, Food and Wine, Waite Research Institute, University of AdelaideAdelaide, SA, Australia.
authors: Tina
authors: T
authors: Bianco-Miotto
authors: Harry Perkins Institute of Medical Research, The University of Western AustraliaPerth, WA, Australia; Plant Energy Biology, Australian Research Council Centre of Excellence, The University of Western AustraliaPerth, WA, Australia.
authors: Sam
authors: S
authors: Buckberry
authors: Robinson Research Institute, University of AdelaideAdelaide, SA, Australia; Bioinformatics Hub, School of Biological Sciences, University of AdelaideAdelaide, SA, Australia.
authors: James
authors: J
authors: Breen
authors: Mater Research Institute, University of Queensland Brisbane, QLD, Australia.
authors: Vicki
authors: V
authors: Clifton
authors: Robinson Research Institute, University of AdelaideAdelaide, SA, Australia; Adelaide Medical School, University of AdelaideAdelaide, SA, Australia.
authors: Cheryl
authors: C
authors: Shoubridge
authors: Robinson Research Institute, University of AdelaideAdelaide, SA, Australia; Adelaide Medical School, University of AdelaideAdelaide, SA, Australia.
authors: Claire T
authors: CT
authors: Roberts
keywords: human; meta-analysis; microarray; organs; sex-biased gene expression