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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams, J. B., Johansen, L. J., Powell, L. D., Quig, D., & Rubin, R. A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC Gastroenterology, 11, 22. https://doi.org/10.1186/1471-230x-11-22
Adès, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., & Bennetts, B. (2006). FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. American Journal of Medical Genetics. Part A, 140(10), 1047–1058. https://doi.org/10.1002/ajmg.a.31202
Al-Haddad, B. J. S., Oler, E., Armistead, B., Elsayed, N. A., Weinberger, D. R., Bernier, R., Burd, I., Kapur, R., Jacobsson, B., Wang, C., Mysorekar, I., Rajagopal, L., & AdamsWaldorf, K. M. (2019). The fetal origins of mental illness. American Journal of Obstetrics and Gynecology, 221(6), 549–562. https://doi.org/10.1016/j.ajog.2019.06.013
Anitha, A., & Thanseem, I. (2015). microRNA and Autism. Advances in Experimental Medicine and Biology, 888, 71–83. https://doi.org/10.1007/978-3-319-22671-2_5
Bakrania, B. A., George, E. M., & Granger, J. P. (2022). Animal models of preeclampsia: Investigating pathophysiology and therapeutic targets. American Journal of Obstetrics and Gynecology, 226(2s), S973-s987. https://doi.org/10.1016/j.ajog.2020.10.025
Bangerter, A., Chatterjee, M., Manyakov, N. V., Ness, S., Lewin, D., Skalkin, A., Boice, M., Goodwin, M. S., Dawson, G., Hendren, R., Leventhal, B., Shic, F., Esbensen, A., & Pandina, G. (2020). Relationship between sleep and behavior in autism spectrum disorder: exploring the impact of sleep variability. Frontiers in Neuroscience, 14, 211. https://doi.org/10.3389/fnins.2020.00211
Beggiato, A., Peyre, H., Maruani, A., Scheid, I., Rastam, M., Amsellem, F., Gillberg, C. I., Leboyer, M., Bourgeron, T., Gillberg, C., & Delorme, R. (2017). Gender differences in autism spectrum disorders: Divergence among specific core symptoms. Autism Research, 10(4), 680–689. https://doi.org/10.1002/aur.1715
Bener, A., & Saleh, N. M. (2013). The impact of socio-economic, lifestyle habits, and obesity in developing of pregnancy-induced hypertension in fast-growing country: Global comparisons. Clinical and Experimental Obstetrics and Gynecology, 40(1), 52–57.
Benschop, L., Duvekot, J. J., & Roeters van Lennep, J. E. (2019). Future risk of cardiovascular disease risk factors and events in women after a hypertensive disorder of pregnancy. Heart, 105(16), 1273–1278. https://doi.org/10.1136/heartjnl-2018-313453
Bjørklund, G., Meguid, N. A., El-Bana, M. A., Tinkov, A. A., Saad, K., Dadar, M., Hemimi, M., Skalny, A. V., Hosnedlová, B., Kizek, R., Osredkar, J., Urbina, M. A., Fabjan, T., El-Houfey, A. A., Kałużna-Czaplińska, J., Gątarek, P., & Chirumbolo, S. (2020). Oxidative stress in autism spectrum disorder. Molecular Neurobiology, 57(5), 2314–2332. https://doi.org/10.1007/s12035-019-01742-2
Bourgeron, T. (2016). Current knowledge on the genetics of autism and propositions for future research. Comptes Rendus Biologies, 339(7–8), 300–307. https://doi.org/10.1016/j.crvi.2016.05.004
Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R., Mane, S. M., Colussi, G., Lebel, M., Gordon, R. D., Semmekrot, B. A., Poujol, A., Välimäki, M. J., De Ferrari, M. E., Sanjad, S. A., Gutkin, M., Karet, F. E., … Lifton, R. P. (2012). Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature, 482(7383), 98–102. https://doi.org/10.1038/nature10814
Brand, J. S., Lawlor, D. A., Larsson, H., & Montgomery, S. (2021). Association between hypertensive disorders of pregnancy and neurodevelopmental outcomes among offspring. JAMA Pediatrics, 175(6), 577–585. https://doi.org/10.1001/jamapediatrics.2020.6856
Brionne, T. C., Tesseur, I., Masliah, E., & Wyss-Coray, T. (2003). Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron, 40(6), 1133–1145. https://doi.org/10.1016/s0896-6273(03)00766-9
Buja, A., Volfovsky, N., Krieger, A. M., Lord, C., Lash, A. E., Wigler, M., & Iossifov, I. (2018). Damaging de novo mutations diminish motor skills in children on the autism spectrum. Proc Natl Acad Sci U S A, 115(8), E1859-e1866. https://doi.org/10.1073/pnas.1715427115
Chaste, P., & Leboyer, M. (2012). Autism risk factors: Genes, environment, and gene-environment interactions. Dialogues in Clinical Neuroscience, 14(3), 281–292. https://doi.org/10.31887/DCNS.2012.14.3/pchaste
Cheroni, C., Caporale, N., & Testa, G. (2020). Autism spectrum disorder at the crossroad between genes and environment: Contributions, convergences, and interactions in ASD developmental pathophysiology. Mol Autism, 11(1), 69. https://doi.org/10.1186/s13229-020-00370-1
Choi, G. B., Yim, Y. S., Wong, H., Kim, S., Kim, H., Kim, S. V., Hoeffer, C. A., Littman, D. R., & Huh, J. R. (2016). The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science, 351(6276), 933–939. https://doi.org/10.1126/science.aad0314
Constantino, J. N., & Todd, R. D. (2005). Intergenerational transmission of subthreshold autistic traits in the general population. Biological Psychiatry, 57(6), 655–660. https://doi.org/10.1016/j.biopsych.2004.12.014
Cotechini, T., Komisarenko, M., Sperou, A., Macdonald-Goodfellow, S., Adams, M. A., & Graham, C. H. (2014). Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. Journal of Experimental Medicine, 211(1), 165–179. https://doi.org/10.1084/jem.20130295
Cui, L., Du, W., Xu, N., Dong, J., Xia, B., Ma, J., Yan, R.,Wang, L., & Feng, F. (2021). Impact of MicroRNAs in interaction with environmental factors on autism spectrum disorder: An exploratory pilot study. Frontiers in Psychiatry, 12, 715481. https://doi.org/10.3389/fpsyt.2021.715481
De Rubeis, S., He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., Kou, Y., Liu, L., Fromer, M., Walker, S., Singh, T., Klei, L., Kosmicki, J., Fu, S.-C., Aleksic, B., Biscaldi, M., Bolton, P. F., Brownfeld, J. M., Cai, J., … Buxbaum, J. D. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515(7526), 209–215. https://doi.org/10.1038/nature13772
Dhillion, P., Wallace, K., Herse, F., Scott, J., Wallukat, G., Heath, J., Mosely, J., Martin, J. N., Dechend, R., & LaMarca, B. (2012). IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 303(4), R353-358. https://doi.org/10.1152/ajpregu.00051.2012
Dong, F., Jiang, J., McSweeney, C., Zou, D., Liu, L., & Mao, Y. (2016). Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects. Human Molecular Genetics, 25(13), 2738–2751. https://doi.org/10.1093/hmg/ddw131
Dong, Z., Chen, W., Chen, C., Wang, H., Cui, W., Tan, Z., Robinson, H., Gao, N., Luo, B., Zhang, L., Zhao, K., Xiong, W.-C., & Mei, L. (2020). CUL3 deficiency causes social deficits and anxiety-like behaviors by impairing excitation-inhibition balance through the promotion of cap-dependent translation. Neuron, 105(3), 475-490.e476. https://doi.org/10.1016/j.neuron.2019.10.035
Douard, E., Zeribi, A., Schramm, C., Tamer, P., Loum, M. A., Nowak, S., Saci, Z., Lord, M. P., Rodríguez-Herreros, B., Jean-Louis, M., Moreau, C., Loth, E., Schumann, G., Pausova, Z., Elsabbagh, M., Almasy, L., Glahn, D. C., Bourgeron, T., Labbe, A., … Jacquemont, S. (2021). Effect sizes of deletions and duplications on autism risk across the genome. American Journal of Psychiatry, 178(1), 87–98. https://doi.org/10.1176/appi.ajp.2020.19080834
Ehninger, D., Sano, Y., de Vries, P. J., Dies, K., Franz, D., Geschwind, D. H., Kaur, M., Lee, Y.-S., Li, W., Lowe, J. K., Nakagawa, J. A., Sahin, M., Smith, K., Whittemore, V., & Silva, A. J. (2012). Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Molecular Psychiatry, 17(1), 62–70. https://doi.org/10.1038/mp.2010.115
Faa, G., Manchia, M., Pintus, R., Gerosa, C., Marcialis, M. A., & Fanos, V. (2016). Fetal programming of neuropsychiatric disorders. Birth Defects Research. Part C, Embryo Today, 108(3), 207–223. https://doi.org/10.1002/bdrc.21139
Figueiró-Filho, E. A., Croy, B. A., Reynolds, J. N., Dang, F., Piro, D., Rätsep, M. T., Forkert, N. D., Paolozza, A., Smith, G. N., & Stroman, P. W. (2017). Diffusion tensor imaging of white matter in children born from preeclamptic gestations. AJNR. American Journal of Neuroradiology, 38(4), 801–806. https://doi.org/10.3174/ajnr.A5064
Fischbach, G. D., & Lord, C. (2010). The Simons Simplex Collection: A resource for identification of autism genetic risk factors. Neuron, 68(2), 192–195. https://doi.org/10.1016/j.neuron.2010.10.006
Gardner, E. J., Sifrim, A., Lindsay, S. J., Prigmore, E., Rajan, D., Danecek, P., Gallone, G., Eberhardt, R. Y., Martin, H. C., Wright, C. F., FitzPatrick, D. R., Firth, H. V., & Hurles, M. E. (2021). Detecting cryptic clinically relevant structural variation in exome-sequencing data increases diagnostic yield for developmental disorders. American Journal of Human Genetics, 108(11), 2186–2194. https://doi.org/10.1016/j.ajhg.2021.09.010
Gill, M., Donohoe, G., & Corvin, A. (2010). What have the genomics ever done for the psychoses? Psychological Medicine, 40(4), 529–540. https://doi.org/10.1017/s0033291709991139
Gotham, K., Risi, S., Pickles, A., & Lord, C. (2007). The Autism Diagnostic Observation Schedule: Revised algorithms for improved diagnostic validity. Journal of Autism and Developmental Disorders, 37(4), 613–627. https://doi.org/10.1007/s10803-006-0280-1
Huisman-van Dijk, H. M., Schoot, R., Rijkeboer, M. M., Mathews, C. A., & Cath, D. C. (2016). The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. Psychiatry Research, 237, 138–146. https://doi.org/10.1016/j.psychres.2016.01.051
Iakoucheva, L. M., Muotri, A. R., & Sebat, J. (2019). Getting to the cores of Autism. Cell, 178(6), 1287–1298. https://doi.org/10.1016/j.cell.2019.07.037
Iossifov, I., Levy, D., Allen, J., Ye, K., Ronemus, M., Lee, Y. H., Yamrom, B., & Wigler, M. (2015). Low load for disruptive mutations in autism genes and their biased transmission. Proc Natl Acad Sci U S A, 112(41), E5600-5607. https://doi.org/10.1073/pnas.1516376112
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Witherspoon, K. T., Vives, L., Patterson, K. E., Smith, J. D., Paeper, B., Nickerson, D. A., Dea, J., Dong, S., Gonzalez, L. E., Mandell, J. D., Mane, S. M., Murtha, M. T., … Wigler, M. (2014). The contribution of de novo coding mutations to autism spectrum disorder. Nature, 515(7526), 216–221. https://doi.org/10.1038/nature13908
Jensen, M., Smolen, C., & Girirajan, S. (2020). Gene discoveries in autism are biased towards comorbidity with intellectual disability. Journal of Medical Genetics, 57(9), 647–652. https://doi.org/10.1136/jmedgenet-2019-106476
Jones, K. L., & Van de Water, J. (2019). Maternal autoantibody related autism: Mechanisms and pathways. Molecular Psychiatry, 24(2), 252–265. https://doi.org/10.1038/s41380-018-0099-0
Kästel, I. S., Vllasaliu, L., Wellnitz, S., Cholemkery, H., Freitag, C. M., & Bast, N. (2021). Repetitive behavior in children and adolescents: psychometric properties of the german version of the repetitive behavior scale-revised. Journal of Autism and Developmental Disorders, 51(4), 1224–1237. https://doi.org/10.1007/s10803-020-04588-z
Kim, J.-W., Park, K., Kang, R. J., Gonzales, E. L., Oh, H. A., Seung, H., Ko, M. J., Cheong, J. H., Chung, C., & Shin, C. Y. (2019a). Gene-environment interaction counterbalances social impairment in mouse models of autism. Science and Reports, 9(1), 11490. https://doi.org/10.1038/s41598-019-47680-w
Kim, J. Y., Son, M. J., Son, C. Y., Radua, J., Eisenhut, M., Gressier, F., Koyanagi, Ai., Carvalho, A. F., Stubbs, B., Solmi, M., Rais, T. B., Lee, K. H., Kronbichler, A., Dragioti, E., Shin, JIl., & Fusar-Poli, P. (2019b). Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence. Lancet Psychiatry, 6(7), 590–600. https://doi.org/10.1016/s2215-0366(19)30181-6
Kosmicki, J. A., Samocha, K. E., Howrigan, D. P., Sanders, S. J., Slowikowski, K., Lek, M., Karczewski, K. J., Cutler, D. J., Devlin, B., Roeder, K., Buxbaum, J. D., Neale, B. M., MacArthur, D. G., Wall, D. P., Robinson, E. B., & Daly, M. J. (2017). Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples. Nature Genetics, 49(4), 504–510. https://doi.org/10.1038/ng.3789
Kwan, V., Unda, B. K., & Singh, K. K. (2016). Wnt signaling networks in autism spectrum disorder and intellectual disability. Journal of Neurodevelopmental Disorders, 8, 45. https://doi.org/10.1186/s11689-016-9176-3
Lai, M. C., Lombardo, M. V., & Baron-Cohen, S. (2014). Autism. Lancet, 383(9920), 896–910. https://doi.org/10.1016/s0140-6736(13)61539-1
Lam, K. S., & Aman, M. G. (2007). The Repetitive Behavior Scale-Revised: Independent validation in individuals with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37(5), 855–866. https://doi.org/10.1007/s10803-006-0213-z
Le Belle, J. E., Sperry, J., Ngo, A., Ghochani, Y., Laks, D. R., López-Aranda, M., Silva, A. J., & Kornblum, H. I. (2014). Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells. Stem Cell Reports, 3(5), 725–734. https://doi.org/10.1016/j.stemcr.2014.09.004
Lefort-Besnard, J., Vogeley, K., Schilbach, L., Varoquaux, G., Thirion, B., Dumas, G., & Bzdok, D. (2020). Patterns of autism symptoms: Hidden structure in the ADOS and ADI-R instruments. Translational Psychiatry, 10(1), 257. https://doi.org/10.1038/s41398-020-00946-8
Li, J., Zhao, T., Zhang, Y., Zhang, K., Shi, L., Chen, Y., Wang, X., & Sun, Z. (2018). Performance evaluation of pathogenicity-computation methods for missense variants. Nucleic Acids Research, 46(15), 7793–7804. https://doi.org/10.1093/nar/gky678
Lindsay, M. E., Schepers, D., Bolar, N. A., Doyle, J. J., Gallo, E., Fert-Bober, J., Kempers, M. J. E., Fishman, E. K., Chen, Y., Myers, L., Bjeda, D., Oswald, G., Elias, A. F., Levy, H. P., Anderlid, B.-M., Yang, M. H., Bongers, E. M. H. F., Timmermans, J., Braverman, A. C., … Loeys, B. L. (2012). Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nature Genetics, 44(8), 922–927. https://doi.org/10.1038/ng.2349
Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Neda Sharifi, F., Lauren, Xu., Myers, L. A., Spevak, P. J., Cameron, D. E., De Backer, J., Hellemans, J., Chen, Y., Davis, E. C., Webb, C. L., … Dietz, H. C. (2005). A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nature Genetics, 37(3), 275–281. https://doi.org/10.1038/ng1511
Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Francesca Faravelli, M., Greco, A., Pyeritz, R. E., Milewicz, D. M., Coucke, P. J., Cameron, D. E., Braverman, A. C., Byers, P. H., … Dietz, H. C. (2006). Aneurysm syndromes caused by mutations in the TGF-beta receptor. New England Journal of Medicine, 355(8), 788–798. https://doi.org/10.1056/NEJMoa055695
Lord, C., Pickles, A., McLennan, J., Rutter, M., Bregman, J., Folstein, S., Fombonne, E., Leboyer, M., & Minshew, N. (1997). Diagnosing autism: analyses of data from the Autism Diagnostic Interview. Journal of Autism and Developmental Disorders, 27(5), 501–517. https://doi.org/10.1023/a:1025873925661
Lyall, K., Croen, L., Julie Daniels, M., Fallin, D., Ladd-Acosta, C., Lee, B. K., Park, B. Y., Snyder, N. W., Schendel, D., Volk, H., Windham, G. C., & Newschaffer, C. (2017). The changing epidemiology of autism spectrum disorders. Annual Review of Public Health, 38, 81–102. https://doi.org/10.1146/annurev-publhealth-031816-044318
Lyall, K., Ning, X., Aschner, J. L., Avalos, L. A., Bennett, D. H., Bilder, D. A., Bush, N. R., Carroll, K. N., Chu, S. H., Croen, L. A., Dabelea, D., Daniels, J. L., Duarte, C., Elliott, A. J., Fallin, M. D., Ferrara, A., Hertz-Picciotto, I., Hipwell, A. E., Jensen, E. T., … Ladd-Acosta, C. (2022). Cardiometabolic pregnancy complications in association with autism-related traits as measured by the social responsiveness scale in ECHO. American Journal of Epidemiology. https://doi.org/10.1093/aje/kwac061
Maher, G. M., O’Keeffe, G. W., Kearney, P. M., Kenny, L. C., Dinan, T. G., Mattsson, M., & Khashan, A. S. (2018). Association of hypertensive disorders of pregnancy with risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis. JAMA Psychiatry, 75(8), 809–819. https://doi.org/10.1001/jamapsychiatry.2018.0854
Mak, L. E., Anne Croy, B., Kay, V., Reynolds, J. N., Rätsep, M. T., Forkert, N. D., Smith, G. N., Paolozza, A., Stroman, P. W., & Figueiró-Filho, E. A. (2018). Resting-state functional connectivity in children born from gestations complicated by preeclampsia: A pilot study cohort. Pregnancy Hypertens, 12, 23–28. https://doi.org/10.1016/j.preghy.2018.02.004
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., Cho, J. H., Guttmacher, A. E., Kong, A., Kruglyak, L., Mardis, E., Rotimi, C. N., Slatkin, M., Valle, D., Whittemore, A. S., … Visscher, P. M. (2009). Finding the missing heritability of complex diseases. Nature, 461(7265), 747–753. https://doi.org/10.1038/nature08494
Marks, D. F. (2010). IQ variations across time, race, and nationality: An artifact of differences in literacy skills. Psychological Reports, 106(3), 643–664. https://doi.org/10.2466/pr0.106.3.643-664
Masi, A., Breen, E. J., Alvares, G. A., Glozier, N., Hickie, I. B., Hunt, A., Hui, J., Beilby, J., Ravine, D., Wray, J., Whitehouse, A. J. O., & Guastella, A. J. (2017). Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder. Mol Autism, 8, 63. https://doi.org/10.1186/s13229-017-0176-2
Matson, J. L., Neal, D., Hess, J. A., Mahan, S., & Fodstad, J. C. (2010). The effect of seizure disorder on symptom presentation in atypically developing children and children with autism spectrum disorders based on the BDI-2. Developmental Neurorehabilitation, 13(5), 310–314. https://doi.org/10.3109/17518421003782192
Mazina, V., Gerdts, J., Trinh, S., Ankenman, K., Ward, T., Dennis, M. Y., Girirajan, S., Eichler, E. E., & Bernier, R. (2015). Epigenetics of autism-related impairment: copy number variation and maternal infection. Journal of Developmental and Behavioral Pediatrics, 36(2), 61–67. https://doi.org/10.1097/dbp.0000000000000126
McEwen, B. S., Gray, J. D., & Nasca, C. (2015). 60 YEARS OF NEUROENDOCRINOLOGY: Redefining neuroendocrinology: Stress, sex and cognitive and emotional regulation. Journal of Endocrinology, 226(2), T67-83. https://doi.org/10.1530/joe-15-0121
Minakova, E., & Warner, B. B. (2018). Maternal immune activation, central nervous system development and behavioral phenotypes. Birth Defects Res, 110(20), 1539–1550. https://doi.org/10.1002/bdr2.1416
Mitchell, E. J., Thomson, D. M., Openshaw, R. L., Bristow, G. C., Dawson, N., Pratt, J. A., & Morris, B. J. (2020). Drug-responsive autism phenotypes in the 16p11 2 deletion mouse model: a central role for gene-environment interactions. Science and Reports, 10(1), 12303. https://doi.org/10.1038/s41598-020-69130-8
Murdoch, J. D., Raubeson, M. J., Jeremy Willsey, A., Gulhan Ercan-Sencicek, A., DiLullo, N. M., Parikshak, N. N., Stein, J. L., Walker, M. F., Ober, G. T., Teran, N. A., Song, Y., El-Fishawy, P., Murtha, R. C., Choi, M., Overton, J. D., Bjornson, R. D., Carriero, N. J., Meyer, K. A., Bilguvar, K., … State, M. W. (2012). De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 485(7397), 237–241. https://doi.org/10.1038/nature10945
Nguyen, H., Chiasson, V. L., Chatterjee, P., Kopriva, S. E., Young, K. J., & Mitchell, B. M. (2013). Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension. Cardiovascular Research, 97(4), 696–704. https://doi.org/10.1093/cvr/cvs422
Norbury, C. F. (2014). Practitioner review: Social (pragmatic) communication disorder conceptualization, evidence and clinical implications. Journal of Child Psychology and Psychiatry, 55(3), 204–216. https://doi.org/10.1111/jcpp.12154
O’Roak, B. J., Stessman, H. A., Boyle, E. A., Witherspoon, K. T., Martin, B., Lee, C., Vives, L., Baker, C., Hiatt, J. B., Nickerson, D. A., Bernier, R., Shendure, J., & Eichler, E. E. (2014). Recurrent de novo mutations implicate novel genes underlying simplex autism risk. Nature Communications, 5, 5595. https://doi.org/10.1038/ncomms6595
Pathak, M., Bennett, A., & Shui, A. M. (2019). Correlates of adaptive behavior profiles in a large cohort of children with autism: The autism speaks Autism Treatment Network registry data. Autism, 23(1), 87–99. https://doi.org/10.1177/1362361317733113
Pati, S., Hashim, K., Brown, B., Fiks, A. G., & Forrest, C. B. (2011). Early identification of young children at risk for poor academic achievement: Preliminary development of a parent-report prediction tool. BMC Health Services Research, 11, 197. https://doi.org/10.1186/1472-6963-11-197
Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D., & Gygi, S. P. (2003). A proteomics approach to understanding protein ubiquitination. Nature Biotechnology, 21(8), 921–926. https://doi.org/10.1038/nbt849
Ponsonby, A.-L., Symeonides, C., Saffery, R., Mueller, J. F., O’Hely, M., Sly, P. D., Wardrop, N., Pezic, A., Mansell, T., Collier, F., Burgner, D., Thompson, K., Vijayasarathy, S., Sugeng, E. J., Dwyer, T., Ranganathan, S., Anderson, P. J., Anderson, V., & Vuillermin, P. (2020). Prenatal phthalate exposure, oxidative stress-related genetic vulnerability and early life neurodevelopment: A birth cohort study. Neurotoxicology, 80, 20–28. https://doi.org/10.1016/j.neuro.2020.05.006
Pugliese, C. E., Anthony, L., Strang, J. F., Dudley, K., Wallace, G. L., & Kenworthy, L. (2015). Increasing adaptive behavior skill deficits from childhood to adolescence in autism spectrum disorder: Role of executive function. Journal of Autism and Developmental Disorders, 45(6), 1579–1587. https://doi.org/10.1007/s10803-014-2309-1
Ra Tsep, M. T., Paolozza, A., Hickman, A. F., Maser, B., Kay, V. R., Mohammad, S., Pudwell, J., Smith, G. N., Brien, D., Stroman, P. W., Adams, M. A., Reynolds, J. N., Croy, B. A., & Forkert, N. D. (2016). Brain structural and vascular anatomy is altered in offspring of pre-eclamptic pregnancies: A pilot study. AJNR. American Journal of Neuroradiology, 37(5), 939–945. https://doi.org/10.3174/ajnr.A4640
Ramaswami, G., & Geschwind, D. H. (2018). Genetics of autism spectrum disorder. Handbook of Clinical Neurology, 147, 321–329. https://doi.org/10.1016/b978-0-444-63233-3.00021-x
Rapanelli, M., Tan, T., Wang, W., Wang, X., Wang, Z.-J., Zhong, P., Frick, L., Qin, L., Ma, K., Jun, Q., & Yan, Z. (2021). Behavioral, circuitry, and molecular aberrations by region-specific deficiency of the high-risk autism gene Cul3. Molecular Psychiatry, 26(5), 1491–1504. https://doi.org/10.1038/s41380-019-0498-x
Roberts, J. M., Pearson, G., Cutler, J., & Lindheimer, M. (2003). Summary of the NHLBI working group on research on hypertension during pregnancy. Hypertension, 41(3), 437–445. https://doi.org/10.1161/01.Hyp.0000054981.03589.E9
Rogge, N., & Janssen, J. (2019). The economic costs of autism spectrum disorder: a literature review. Journal of Autism and Developmental Disorders, 49(7), 2873–2900. https://doi.org/10.1007/s10803-019-04014-z
Ronemus, M., Iossifov, I., Levy, D., & Wigler, M. (2014). The role of de novo mutations in the genetics of autism spectrum disorders. Nature Reviews Genetics, 15(2), 133–141. https://doi.org/10.1038/nrg3585
Ruo-Ting, X., Chang, Q.-X., Wang, Q.-Q., Zhang, J., Xia, L.-X., Zhong, N., Yan-Hong, Y., Zhong, M., & Huang, Q.-T. (2018). Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies. Oncotarget, 9(1), 1291–1301. https://doi.org/10.18632/oncotarget.23030
Sanders, S. J., Xin He, A., Jeremy Willsey, A., Ercan-Sencicek, G., Samocha, K. E., Ercument Cicek, A., Murtha, M. T., Bal, V. H., Bishop, S. L., Dong, S., Goldberg, A. P., Jinlu, C., Keaney, J. F., Klei, L., Mandell, J. D., Moreno-De-Luca, D., Poultney, C. S., Robinson, E. B., Smith, L., … State, M. W. (2015). Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron, 87(6), 1215–1233. https://doi.org/10.1016/j.neuron.2015.09.016
Santini, E., Huynh, T., MacAskill, A. F., Carter, A. G., Pierre, P., Ruggero, D., Kaphzan, H., & Klann, E. (2013). Exaggerated translation causes synaptic and behavioural aberrations associated with autism. Nature, 493(7432), 411–415. https://doi.org/10.1038/nature11782
Satterstrom, F. K., Kosmicki, J. A., Wang, J., Breen, M. S., De Rubeis, S., An, J.-Y., Peng, M., Collins, R., Grove, J., Klei, L., Stevens, C., Reichert, J., Mulhern, M. S., Artomov, M., Gerges, S., Sheppard, B., Xu, X., Bhaduri, A., Norman, U., … Walters, R. K. (2020). Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell, 180(3), 568-584.e523. https://doi.org/10.1016/j.cell.2019.12.036
Savitz, D. A., Danilack, V. A., Engel, S. M., Elston, B., & Lipkind, H. S. (2014). Descriptive epidemiology of chronic hypertension, gestational hypertension, and preeclampsia in New York State, 1995–2004. Maternal and Child Health Journal, 18(4), 829–838. https://doi.org/10.1007/s10995-013-1307-9
Schneider, S., Freerksen, N., Maul, H., Roehrig, S., Fischer, B., & Hoeft, B. (2011). Risk groups and maternal-neonatal complications of preeclampsia–current results from the national German perinatal quality registry. Journal of Perinatal Medicine, 39(3), 257–265. https://doi.org/10.1515/jpm.2011.010
Schwartzer, J. J., Careaga, M., Onore, C. E., Rushakoff, J. A., Berman, R. F., & Ashwood, P. (2013). Maternal immune activation and strain specific interactions in the development of autism-like behaviors in mice. Translational Psychiatry, 3(3), e240. https://doi.org/10.1038/tp.2013.16
Jonathan Sebat, B., Lakshmi, D. M., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., Leotta, A., Pai, D., Zhang, R., Lee, Y.-H., Hicks, J., Spence, S. J., Lee, A. T., Puura, K., Lehtimäki, T., Ledbetter, D., … Wigle, M. (2007). Strong association of de novo copy number mutations with autism. Science, 316(5823), 445–449. https://doi.org/10.1126/science.1138659
Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience, 27(40), 10695–10702. https://doi.org/10.1523/jneurosci.2178-07.2007
Sparrow, S. S., Cicchetti, D., & Balla, D. A. (2005). Vineland Adaptive Behavior Scales (2nd ed.): Pearson
Stephens, K., O’Loughlin, R., Green, J. L., Anderson, V., Rinehart, N., Nicholson, J. M., Hazell, P., Silk, T. J., Efron, D., & Sciberras, E. (2021). The association between autism symptoms and child functioning in a sample with ADHD recruited from the community. Journal of Attention Disorders, 25(8), 1129–1134. https://doi.org/10.1177/1087054719886352
Stessman, H. A. F., Xiong, B., Coe, B. P., Wang, T., Hoekzema, K., Fenckova, M., Kvarnung, M., Gerdts, J., Trinh, S., Cosemans, N., Vives, L., Lin, J., Turner, T. N., Santen, G., Ruivenkamp, C., Kriek, M., van Haeringen, A., Aten, E., Friend, K., … Eichler, E. E. (2017). Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nature Genetics, 49(4), 515–526. https://doi.org/10.1038/ng.3792
Travers, B. G., Powell, P. S., Klinger, L. G., & Klinger, M. R. (2013). Motor difficulties in autism spectrum disorder: Linking symptom severity and postural stability. Journal of Autism and Developmental Disorders, 43(7), 1568–1583. https://doi.org/10.1007/s10803-012-1702-x
Turner, T. N., Coe, B. P., Dickel, D. E., Hoekzema, K., Nelson, B. J., Zody, M. C., Kronenberg, Z. N., Hormozdiari, F., Raja, A., Pennacchio, L. A., Darnell, R. B., & Eichler, E. E. (2017). Genomic patterns of de novo mutation in simplex autism. Cell, 171(3), 710-722.e712. https://doi.org/10.1016/j.cell.2017.08.047
Umesawa, M., & Kobashi, G. (2017). Epidemiology of hypertensive disorders in pregnancy: Prevalence, risk factors, predictors and prognosis. Hypertension Research, 40(3), 213–220. https://doi.org/10.1038/hr.2016.126
Wang, H., László, K. D., Gissler, M., Li, F., Zhang, J., Yu, Y., & Li, J. (2021). Maternal hypertensive disorders and neurodevelopmental disorders in offspring: A population-based cohort in two Nordic countries. European Journal of Epidemiology, 36(5), 519–530. https://doi.org/10.1007/s10654-021-00756-2
Webb, S. J., Garrison, M. M., Bernier, R., McClintic, A. M., King, B. H., & Mourad, P. D. (2017). Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound. Autism Research, 10(3), 472–484. https://doi.org/10.1002/aur.1690
Woodhead, G. J., Mutch, C. A., Olson, E. C., & Chenn, A. (2006). Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation. Journal of Neuroscience, 26(48), 12620–12630. https://doi.org/10.1523/jneurosci.3180-06.2006
Yi, J. J., Barnes, A. P., Hand, R., Polleux, F., & Ehlers, M. D. (2010). TGF-beta signaling specifies axons during brain development. Cell, 142(1), 144–157. https://doi.org/10.1016/j.cell.2010.06.010
Ying Zhu, A. M. M., Sousa, T. G., Skarica, M., Li, M., Santpere, G., Esteller-Cucala, P., Juan, D., Ferrández-Peral, L., Gulden, F. O., Yang, M., Miller, D. J., Marques-Bonet, T., Kawasawa, Y. I., Zhao, H., & Sestan, N. (2018). Spatiotemporal transcriptomic divergence across human and macaque brain development. Science. https://doi.org/10.1126/science.aat8077
Zhang, Q., Song, Y., Huang, X., Tan, Y., Zhu, C., Wang, Y.-L., Wang, H., Lin, H.-Y., Jiejun, F., & Wang, H. (2015). New insights into the function of Cullin 3 in trophoblast invasion and migration. Reproduction, 150(2), 139–149. https://doi.org/10.1530/rep-15-0126
Zhao, G., Li, K., Li, B., Wang, Z., Fang, Z., Wang, X., Zhang, Y., Luo, T., Zhou, Q., Wang, L., Xie, Y., Wang, Y., Chen, Q., Xia, L., Tang, Y., Tang, B., Xia, K., & Li, J. (2020). Gene4Denovo: an integrated database and analytic platform for de novo mutations in humans. Nucleic Acids Research, 48(D1), D913-d926. https://doi.org/10.1093/nar/gkz923
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.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors have no conflict of interest to declare.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
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
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10803-022-05824-4