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

Samuel C. Lee, Thomas P. Quinn, Jerry Lai, Sek Won Kong, Irva Hertz-Picciotto, Stephen J. Glatt, Tamsyn M. Crowley, Svetha Venkatesh, Thin Nguyen

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Autistic Disorder
Biomarkers
Inborn Genetic Diseases
Brain
Transcriptome
Meta-Analysis
RNA
Autism Spectrum Disorder
Genes

Keywords

  • ASD
  • autism
  • biomarkers
  • sex-specific
  • transcriptome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Solving for X : Evidence for sex-specific autism biomarkers across multiple transcriptomic studies. / Lee, Samuel C.; Quinn, Thomas P.; Lai, Jerry; Kong, Sek Won; Hertz-Picciotto, Irva; Glatt, Stephen J.; Crowley, Tamsyn M.; Venkatesh, Svetha; Nguyen, Thin.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 01.01.2018.

Research output: Contribution to journalArticle

Lee, Samuel C. ; Quinn, Thomas P. ; Lai, Jerry ; Kong, Sek Won ; Hertz-Picciotto, Irva ; Glatt, Stephen J. ; Crowley, Tamsyn M. ; Venkatesh, Svetha ; Nguyen, Thin. / Solving for X : Evidence for sex-specific autism biomarkers across multiple transcriptomic studies. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2018.
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