Camilo Briones-Valdivieso , Francisco Córdova , Heidy Kaune , Juan F. Montiel
{"title":"自闭症谱系障碍遗传风险候选者的激素和性别特异性功能基因组途径:性别机会效应的证据","authors":"Camilo Briones-Valdivieso , Francisco Córdova , Heidy Kaune , Juan F. Montiel","doi":"10.1016/j.yhbeh.2025.105795","DOIUrl":null,"url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors contribute to ASD, there is growing evidence that sex-specific endocrine pathways, particularly those involving sex hormones, may play a critical role in ASD etiology. This study aimed to investigate the functional network robustness and annotations of autism spectrum disorder genetic risk candidates (ASD-GRCs), with a focus on endocrine pathways and their impact on network connectivity. Using data from the Simon's Foundation Autism Research Initiative (SFARI) and functional network analysis via the STRING database, we assessed the connectivity of ASD-related genes by randomly subtracting sets of genes from the whole ASD gene network in subsets associated with androgen-testosterone, estrogen-progesterone, and other hormone pathways.</div><div>Our findings reveal a significant “sex-over-chance” association, with androgen- and estrogen-related gene subsets showing marked connectivity within the ASD gene network compared to non-sex hormone genes. These results suggest that sex hormones may uniquely influence ASD-related neural development, providing support for the “female protective effect” and the androgen-driven model of ASD. Additional analyses of other hormonal pathways, such as oxytocin and cortisol, showed a lower connectivity impact, reinforcing the distinctive role of sex hormones in ASD. This study highlights the potential of endocrine-focused genetic analysis in understanding ASD, emphasizing sex-specific biological mechanisms that may inform future diagnostic and therapeutic strategies.</div></div>","PeriodicalId":13001,"journal":{"name":"Hormones and Behavior","volume":"174 ","pages":"Article 105795"},"PeriodicalIF":2.4000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hormonal and sex-specific functional genomic pathways of genetic risk candidates in autism spectrum disorder: evidence of sex-over-chance effects\",\"authors\":\"Camilo Briones-Valdivieso , Francisco Córdova , Heidy Kaune , Juan F. Montiel\",\"doi\":\"10.1016/j.yhbeh.2025.105795\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors contribute to ASD, there is growing evidence that sex-specific endocrine pathways, particularly those involving sex hormones, may play a critical role in ASD etiology. This study aimed to investigate the functional network robustness and annotations of autism spectrum disorder genetic risk candidates (ASD-GRCs), with a focus on endocrine pathways and their impact on network connectivity. Using data from the Simon's Foundation Autism Research Initiative (SFARI) and functional network analysis via the STRING database, we assessed the connectivity of ASD-related genes by randomly subtracting sets of genes from the whole ASD gene network in subsets associated with androgen-testosterone, estrogen-progesterone, and other hormone pathways.</div><div>Our findings reveal a significant “sex-over-chance” association, with androgen- and estrogen-related gene subsets showing marked connectivity within the ASD gene network compared to non-sex hormone genes. These results suggest that sex hormones may uniquely influence ASD-related neural development, providing support for the “female protective effect” and the androgen-driven model of ASD. Additional analyses of other hormonal pathways, such as oxytocin and cortisol, showed a lower connectivity impact, reinforcing the distinctive role of sex hormones in ASD. This study highlights the potential of endocrine-focused genetic analysis in understanding ASD, emphasizing sex-specific biological mechanisms that may inform future diagnostic and therapeutic strategies.</div></div>\",\"PeriodicalId\":13001,\"journal\":{\"name\":\"Hormones and Behavior\",\"volume\":\"174 \",\"pages\":\"Article 105795\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hormones and Behavior\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0018506X25001217\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormones and Behavior","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0018506X25001217","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Hormonal and sex-specific functional genomic pathways of genetic risk candidates in autism spectrum disorder: evidence of sex-over-chance effects
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by substantial sex differences in prevalence, with males more frequently diagnosed than females. While genetic and environmental factors contribute to ASD, there is growing evidence that sex-specific endocrine pathways, particularly those involving sex hormones, may play a critical role in ASD etiology. This study aimed to investigate the functional network robustness and annotations of autism spectrum disorder genetic risk candidates (ASD-GRCs), with a focus on endocrine pathways and their impact on network connectivity. Using data from the Simon's Foundation Autism Research Initiative (SFARI) and functional network analysis via the STRING database, we assessed the connectivity of ASD-related genes by randomly subtracting sets of genes from the whole ASD gene network in subsets associated with androgen-testosterone, estrogen-progesterone, and other hormone pathways.
Our findings reveal a significant “sex-over-chance” association, with androgen- and estrogen-related gene subsets showing marked connectivity within the ASD gene network compared to non-sex hormone genes. These results suggest that sex hormones may uniquely influence ASD-related neural development, providing support for the “female protective effect” and the androgen-driven model of ASD. Additional analyses of other hormonal pathways, such as oxytocin and cortisol, showed a lower connectivity impact, reinforcing the distinctive role of sex hormones in ASD. This study highlights the potential of endocrine-focused genetic analysis in understanding ASD, emphasizing sex-specific biological mechanisms that may inform future diagnostic and therapeutic strategies.
期刊介绍:
Hormones and Behavior publishes original research articles, reviews and special issues concerning hormone-brain-behavior relationships, broadly defined. The journal''s scope ranges from laboratory and field studies concerning neuroendocrine as well as endocrine mechanisms controlling the development or adult expression of behavior to studies concerning the environmental control and evolutionary significance of hormone-behavior relationships. The journal welcomes studies conducted on species ranging from invertebrates to mammals, including humans.