Solving for X: Evidence for sex-specific autism biomarkers across multiple transcriptomic studies.
Am J Med Genet B Neuropsychiatr Genet
; 180(6): 377-389, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30520558
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caracteres Sexuais
/
Redes Reguladoras de Genes
/
Transtorno do Espectro Autista
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Assunto da revista:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália