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Title
Solving for X: Evidence for sex-specific autism biomarkers across multiple transcriptomic studies
Author(s)
Lee, Samuel C
Quinn, Thomas P
Lai, Jerry
Kong, Sek Won
Hertz-Picciotto, Irva
Glatt, Stephen J
Venkatesh, Svetha
Thin Nguyen
Publication Date
2019-09
Early Online Version
Abstract
<p>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 characterize their function, we present an analysis of a single paired-end postmortem 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 postmortem 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.</p>
Publication Type
Journal Article
Source of Publication
American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 180(6), p. 377-389
Publisher
John Wiley & Sons, Inc
Socio-Economic Objective (SEO) 2020
2018-12-06
Place of Publication
United States of America
ISSN
1552-485X
1552-4841
Fields of Research (FoR) 2020
Socio-Economic Objective (SEO) 2020
Peer Reviewed
Yes
HERDC Category Description
Peer Reviewed
Yes
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