ArticleMolecular autism2021
Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts.
Article in Molecular autism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Dissecting the shared genetic architecture between testosterone traits and attention-deficit/hyperactivity disorder.European child & adolescent psychiatry · 2026Article
- Measuring sexual dimorphism in human faces.Journal of anatomy · 2026Article
- The prenatal sex steroid theory of autism after 25 years.Nature human behaviour · 2026Review
- Perinatal hyperandrogenization and immune activation in rodents model subtypes of autism.Translational psychiatry · 2026Article
- Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice.eNeuro · 2025Article
- The Placental Steroid Hypothesis of Human Brain Evolution.Evolutionary anthropology · 2025Review
- Sex and gender in neurodevelopmental conditions.Nature reviews. Neurology · 2023Review
- Analysis of salivary steroid hormones in boys with autism spectrum disorder.BMC psychiatry · 2023Article
- Maternal androgens and autism spectrum disorder in the MARBLES prospective cohort study.Research in autism spectrum disorders · 2022Article
- An investigation of a novel broad autism phenotype: increased facial masculinity among parents of children on the autism spectrum.Proceedings. Biological sciences · 2022Article
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18 authors.
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Abstract
backgroundNeurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear.
methodsHere, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores.
resultsWe found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules.
conclusionsThese findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.
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