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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,
HertzPicciotto Irva,
Glatt Stephen J.,
Crowley Tamsyn M.,
Venkatesh Svetha,
Nguyen Thin
Publication year - 2019
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32701
Subject(s) - concordance , transcriptome , autism , phenotype , biomarker , biology , proband , autism spectrum disorder , microarray , microarray analysis techniques , sex characteristics , genetics , gene , bioinformatics , computational biology , gene expression , psychology , developmental psychology , mutation
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.