Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study

Objectives: To investigate whether second-to-fourth digit ratio (2D:4D), a measure commonly used as a proxy for fetal testosterone exposure, is associated with autism spectrum disorders (ASDs), as predicted by the extreme male brain theory of autism. Design: A birth cohort study. Setting: The Avon Longitudinal Study of Parents and Children (ALSPAC). Participants: 6015 ALSPAC children with data on digit ratio, at least 1 outcome measure and information on potential confounding variables (parental occupational class, maternal education and age at digit ratio measurement). Digit ratio was measured by the photocopy and calliper method. Outcomes: ASD diagnosis (cases were identified previously by record linkage or maternal report) and 4 measures that combine optimally within ALSPAC to predict ASD: the Children's Communication Checklist (coherence subscale), the Social and Communication Disorders Checklist, a repetitive behaviour measure, and the Emotionality, Activity and Sociability scale (sociability subscale). These measures were dichotomised, with approximately 10% defined as the 'risk' group. Results: Using logistic regression, we examined the association of 2D: 4D with ASDs and 4 dichotomised ASD traits. Covariates were occupational class, maternal education and age at 2D: 4D measurement. 2D: 4D was not associated with ASDs in males (adjusted OR per 1 SD increase in mean 2D: 4D, 0.88 (95% CI 0.65 to 1.21), p= 0.435) or females (adjusted OR= 1.36 (95% CI 0.81 to 2.28), p= 0.245). Similar results were observed after adjustment for IQ. There was 1 weak association between reduced coherence and increased left 2D: 4D in males, in the opposite direction to that predicted by the extreme male brain theory (adjusted OR= 1.15 (95% CI 1.02 to 1.29), p= 0.023). Given multiple comparisons, this is consistent with chance. Conclusions: In this population-based study, there was no strong evidence of an association between 2D: 4D and ASD diagnosis or traits, although the CIs were wide. These results are not consistent with the extreme male brain theory.