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

Details

• Alternative Title:
  Am J Med Genet B Neuropsychiatr Genet
• Personal Author:
  Lee, Samuel C. ; Quinn, Thomas P. ; Lai, Jerry ; Kong, Sek Won ; Hertz-Picciotto, Irva ; Glatt, Stephen J. ; Crowley, Tamsyn M. ; Venkatesh, Svetha ; Nguyen, Thin
• Description:
  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.
• Subjects:
  Autism Spectrum Disorder Autistic Disorder Biomarkers Brain Female Gene Expression Profiling Gene Regulatory Networks Humans Male Sequence Analysis, RNA Sex Characteristics Siblings Transcriptome

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• Keywords:
  ASD Autism Biomarkers Sex-specific Transcriptome
• Source:
  Am J Med Genet B Neuropsychiatr Genet. 180(6):377-389
• Pubmed ID:
  30520558
• Pubmed Central ID:
  PMC6551334
• Document Type:
  Journal Article
• Funding:
  P01 ES011269/ES/NIEHS NIH HHSUnited States/ ; R01 ES015359/ES/NIEHS NIH HHSUnited States/ ; U54 HD079125/HD/NICHD NIH HHSUnited States/ ; RD83543201/EPA/EPAUnited States/ ; P30 ES023513/ES/NIEHS NIH HHSUnited States/ ; UG3 OD023365/OD/NIH HHSUnited States/ ; UG3 OD023365/CD/ODCDC CDC HHSUnited States/ ; R01 MH107205/MH/NIMH NIH HHSUnited States/ ; P50 HD103526/HD/NICHD NIH HHSUnited States/
• Volume:
  180
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:9b35c85432ea7077362701b6288e08b5b4d90c5724751711d3885f069df336cfb14cf5e9e3415d79e2a8bcd2b8f3080aca3dad6948aad26c92fa7c3bda06bcc7
• Download URL:
  https://stacks.cdc.gov/view/cdc/80364/cdc_80364_DS1.pdf
• File Type:
  [PDF - 970.70 KB ]