Solving for X: Evidence for sex‐specific autism biomarkers across multiple transcriptomic studies
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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.
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Evidence from animal and human studies suggests that endocrine-disrupting compounds such as bisphenol A affect neurodevelopmental outcomes via immune cell functioning, although most human studies are limited by imprecise measures of exposure.
“Evidence from animal and human studies also suggests that endocrine-disrupting compounds such as bisphenol A affect neurodevelopmental outcomes via immune cell functioning274, although most human studies are limited by imprecise measures of exposure and more rigorous epidemiological studies are warranted275.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [274]
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- Authors
- Lee, S. C., Quinn, T. P., Lai, J., Kong, S. W., Hertz‐Picciotto, I., Glatt, S. J., Crowley, T. M., Venkatesh, S., & Nguyen, T.
- Affiliations
- Centre for Pattern Recognition and Data Analytics (PRaDA) Deakin University Geelong Australia
- Deakin University (AU)
- Boston Children's Hospital (US)
- University of California, Davis (US)
- SUNY Upstate Medical University (US)
- Corresponding author
- Quinn, Thomas P.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2018-12-06
- Volume
- 180
- Issue
- 6
- Pages
- 377-389
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC6551334
- OpenAlex
- W2950468148
- Cited by
- 14
- References
- 65
- Citations by year
- 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- RUNE (Research UNE) (submittedVersion)
- Funders
- Foundation for the National Institutes of Health (R01MH107205UG3OD023365)
- National Institute of Environmental Health Sciences (1P30ES0235131R01ES0153592R01ES0153593P01ES011269, 3P01ES011269, 1P30ES023513, 2R01ES015359, 1R01ES015359)
- U.S. Environmental Protection Agency (RD83543201)
- Korea National Institute of Health (UG3OD023365, R01MH107205)
- Australian Research Council (LP140100240)
- Environmental Protection Agency (RD83543201)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- autism spectrum disorder, sex differences, sex-specific biomarkers, gene expression dysregulation, blood transcriptome, pathway analysis, genetic etiology
- MeSH terms
- Autism Spectrum Disorder, Autistic Disorder, Brain, Female, Humans, Male, Sex Characteristics, Biomarkers, Sequence Analysis, RNA, Gene Expression Profiling, Siblings, Gene Regulatory Networks, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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