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

Title
Solving for X: Evidence for sex-specific autism biomarkers across multiple transcriptomic studies
Publication Date
2019-09
Author(s)
Lee, Samuel C
Quinn, Thomas P
Lai, Jerry
Kong, Sek Won
Hertz-Picciotto, Irva
Glatt, Stephen J
Crowley, Tamsyn M
Venkatesh, Svetha
Thin Nguyen
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
John Wiley & Sons, Inc
Place of publication
United States of America
DOI
10.1002/ajmg.b.32701
UNE publication id
une:1959.11/51841
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 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.

Link
Citation
American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 180(6), p. 377-389
ISSN
1552-485X
1552-4841
Pubmed ID
30520558
Start page
377
End page
389

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