RT Journal Article
SR Electronic
T1 Transcript levels of 4 genes in umbilical cord blood are predictive of later autism development: a longitudinal follow-up study
JF Journal of Psychiatry and Neuroscience
JO JPN
FD Canadian Medical Association
SP E334
OP E344
DO 10.1503/jpn.230046
VO 48
IS 5
A1 Jia, Qingzheng
A1 Li, Huilin
A1 Wang, Min
A1 Wei, Chongxia
A1 Xu, Lichao
A1 Ye, Lin
A1 Wang, Chunjun
A1 Ke, Shaofeng
A1 Li, Ling
A1 Yao, Paul
YR 2023
UL http://jpn.ca/content/48/5/E334.abstract
AB Background: Over recent decades, autism spectrum disorder (ASD) has been of increasing epidemiological importance, given the substantial increase in its prevalence; at present, clinical diagnosis is possible only after 2 years of age. In this study, we sought to develop a potential predictive model for ASD screening.Methods: We conducted a longitudinal follow-up study of newborns over 3 years. We measured transcript levels of 4 genes (superoxide dismutase-2 [SOD2], retinoic acid–related orphan receptor-α [RORA], G protein–coupled estrogen receptor-1 [GPER], progesterone receptor [PGR]), 2 oxidative stress markers and epigenetic marks at the RORA promoter in case–control umbilical cord blood mononuclear cell (UCBMC) samples.Results: We followed 2623 newborns; we identified 41 children with ASD, 63 with delayed development and 2519 typically developing children. We matched the 41 children with ASD to 41 typically developing children for UCBMC measurements. Our results showed that children with ASD had significantly higher levels of H3K9me3 histone modifications at the RORA promoter and oxidative stress in UCBMC than typically developing children; children with delayed development showed no significant differences. Children with ASD had significantly lower expression of SOD2, RORA and GPER, but higher PGR expression than typically developing children. We established a model based on these 4 candidate genes, and achieved an area under the curve of 87.0% (standard deviation 3.9%) with a sensitivity of 1.000 and specificity of 0.854 to predict ASD in UCBMC.Limitations: Although the gene combinations produced a good pass/fail cut-off value for ASD evaluation, relatively few children in our study sample had ASD.Conclusion: The altered gene expression in UCBMC can predict later autism development, possibly providing a predictive model for ASD screening immediately after birth.All data are available in either the manuscript or supplementary information.