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 language | English (US) |
|---|---|
| Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Solving for X
T2 - Evidence for sex-specific autism biomarkers across multiple transcriptomic studies
AU - Lee, Samuel C.
AU - Quinn, Thomas P.
AU - Lai, Jerry
AU - Kong, Sek Won
AU - Hertz-Picciotto, Irva
AU - Glatt, Stephen J.
AU - Crowley, Tamsyn M.
AU - Venkatesh, Svetha
AU - Nguyen, Thin
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - ASD
KW - autism
KW - biomarkers
KW - sex-specific
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85058017188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058017188&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32701
DO - 10.1002/ajmg.b.32701
M3 - Article
C2 - 30520558
AN - SCOPUS:85058017188
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
SN - 1552-4841
ER -