Abstract
Genetic factors, particularly, de novo variants (DNV), and an environment factor, exposure to pregnancy-induced hypertension (PIH), were reported to be associated with risk of autism spectrum disorder (ASD); however, how they jointly affect the severity of ASD symptom is unclear. We assessed the severity of core ASD symptoms affected by functional de novo variants or PIH. We selected phenotype data from Simon‘s Simplex Collection database, used genotypes from previous studies, and created linear regression models. We found that ASD patients carrying DNV with PIH exposure had increased adaptive and cognitive ability, decreased social problems, and enhanced repetitive behaviors; however, there was no difference in patients without DNV between those with or without PIH exposure. In addition, the DNV genes carried by patients exposed to PIH were enriched in ubiquitin-dependent proteolytic processes, highlighting how candidate genes in pathways and environments interact. The results indicate the joint contribution of DNV and PIH to ASD.
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Acknowledgements
Grant sponsor: Hunan Natural Science Foundation Outstanding Youth Fund; Grant number: 2020JJ3059 to J. Li. Grant sponsor: Science and Technology Major Project of Hunan Provincial Science and Technology Department; Grant number: 2018SK1030 to K. Xia. Grant sponsor: Hunan Youth Science and Technology Innovation Talent Project; Grant number: 2020RC3060 to J. Li. Grant sponsor: National Natural Science Foundation of China; Grant number: 81730036 to K. Xia, and 81801133 to J. Li. We gratefully acknowledge the Bioinformatics Center && National Clinical Research Centre for Geriatric Disorders && Department of Geriatrics, Xiangya Hospital, Central South University and High Performance Computing Center of Central South University for their support. We gratefully acknowledge the SSC database for providing relevant data for this study. If someone is interested in this research, the SSC population data set is available through the website http://base.sfari.org.
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Wang, X., Ling, Z., Luo, T. et al. Severity of Autism Spectrum Disorder Symptoms Associated with de novo Variants and Pregnancy-Induced Hypertension. J Autism Dev Disord 54, 749–764 (2024). https://doi.org/10.1007/s10803-022-05824-4
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DOI: https://doi.org/10.1007/s10803-022-05824-4