Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts.
Mol Autism
; 12(1): 43, 2021 06 09.
Article
en En
| MEDLINE
| ID: mdl-34108004
ABSTRACT
BACKGROUND:
Neurodevelopmental 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.METHODS:
Here, 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.RESULTS:
We 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.CONCLUSIONS:
These 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastorno del Espectro Autista
/
Andrógenos
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Autism
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos