Umbilical Cord Blood Androgen Related Gene Expression and Risk of Autism Spectrum Disorder in an Enriched Pregnancy Cohort

Thursday, May 11, 2017: 12:00 PM-1:40 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
K. M. Bakulski1, B. Y. Park2, J. I. Feinberg3, L. A. Croen4, I. Hertz-Picciotto5, C. Ladd-Acosta6, C. J. Newschaffer7, H. E. Volk6 and M. D. Fallin8, (1)University of Michigan, Ann Arbor, MI, (2)Johns Hopkins Bloomberg School of Public Health, Baltimore,, MD, (3)Johns Hopkins University, Baltimore, MD, (4)Kaiser Permanente Division of Research, Oakland, CA, (5)University of California at Davis, Davis, CA, (6)Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (7)Drexel University A.J. Drexel Autism Institute, Philadelphia, PA, (8)Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD
Background: Autism spectrum disorder (ASD) affects more than 1% of children in the United States. The male-to-female ASD prevalence ratio is roughly 4:1, but the biological mechanisms are poorly understood. An explicit focus on etiologic pathways underlying this sex difference, such as the hormonal in uteroenvironment, may help elucidate causes of ASD.

Objectives: To examine the relationship between androgen levels and RNA expression in cord blood and the relationship to ASD diagnosis at 36-months.

Methods: Genome-wide RNA expression was measured in 155 cord blood samples from the Early Autism Risk Longitudinal Investigation (EARLI), an enriched-risk pregnancy cohort of families with a child previously diagnosed with ASD. Families were recruited from 4 study sites (Drexel University, University of California Davis & MIND Institute, Johns Hopkins University, and Kaiser Permanente in Northern California). RNA expression was assessed using the Affymetrix Human Gene 2.0 array. Cord blood androgen levels (testosterone, androstenedione, dehydroepiandrosterone) were also measured. Standard RNA data quality control and RMA normalization pipelines were implemented. Surrogate variable analysis was used to adjust for potential cell-type and batch effects. We tested for gene expression differences by androgen levels stratified by sex. We further examined whether expression of androgen related genes, including steroidogenic pathway genes related to androgen synthesis and degradation, were associated with ASD risk. ASD diagnosis at 36-months and cord blood RNA and androgen data were available in 116 samples (20 ASD, 46 non-typical development, and 50 typical development).

Results: Cord blood gene expression differences between typically developing children and children with ASD did not reach genome wide significance (FDR q-value<0.05) adjusting for multiple comparisons in either sex. We will report top-ranked differentially expressed genes by androgen and will explore implicated regions for their potential functional relevance to ASD risk.

Conclusions: This study describes differences in RNA expression by androgen levels, and further examines the role of androgen-related genes in ASD risk, which may play a role in the ASD sex disparity.

See more of: Genetics
See more of: Genetics