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bioRxiv · 10.1101/309518

Solving for X: evidence for sex-specific autism biomarkers across multiple transcriptomic studies

Lee, S. C.·Quinn, T. P.·Lai, J.·Kong, S. W.·Hertz-Picciotto, I.·Glatt, S. J.·Crowley, T. M.·Venkatesh, S.·Nguyen, T.
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Abstract

Autism spectrum disorder (ASD) is a markedly heterogeneous condition with a varied phenotypic presentation. Its high concordance among siblings, as well as its clear association with specific genetic disorders, both point to a strong genetic etiology. However, the molecular basis of ASD is still poorly understood, although recent studies point to the existence of sex-specific ASD pathophysiologies and biomarkers. Despite this, little is known about how exactly sex influences the gene expression signatures of ASD probands. In an effort to identify sex-dependent biomarkers (and characterise their function), we present an analysis of a single paired-end post-mortem brain RNA-Seq data set and a meta-analysis of six blood-based microarray data sets. Here, we identify several genes with sex-dependent dysregulation, and many more with sex-independent dysregulation. Moreover, through pathway analysis, we find that these sex-independent biomarkers have substantially different biological roles than the sex-dependent biomarkers, and that some of these pathways are ubiquitously dysregulated in both post-mortem brain and blood. We conclude by synthesizing the discovered biomarker profiles with the extant literature, by highlighting the advantage of studying sex-specific dysregulation directly, and by making a call for new transcriptomic data that comprise large female cohorts.

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Lee, S. C., Quinn, T. P., Lai, J., Kong, S. W., Hertz-Picciotto, I., Glatt, S. J., Crowley, T. M., Venkatesh, S., Nguyen, T.. 2018-04-28. Solving for X: evidence for sex-specific autism biomarkers across multiple transcriptomic studies. https://doi.org/10.1101/309518

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