Digit Ratio and Autism Spectrum Disorders: Results from the Avon Longitudinal Study of Parents and Children (ALSPAC) Birth Cohort

Background: Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders with a preponderance amongst males. The extreme male brain (EMB) theory of autism suggests that increased fetal testosterone exposure may predispose to an exaggerated male cognitive profile. Second-to-fourth digit ratio (2D:4D), a sexually dimorphic trait, is used as a fetal testosterone proxy: lower, masculinized 2D:4D may imply increased exposure.

Objectives:  We sought to investigate the association between 2D:4D and ASD, including ASD traits, in the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK-based population study.

Methods: 6015 children were studied (including 56 with ASD). Using logistic regression, we examined for association of 2D:4D with ASDs and four dichotomized ASD traits: the Children’s Communication Checklist (coherence subscale), the Social and Communication Disorders Checklist, a measure of repetitive behavior, and the Emotionality, Activity and Sociability scale (sociability subscale). Covariates were occupational class, maternal education and age at 2D:4D measurement. 

Results: 2D:4D was not associated with ASDs in males (adjusted odds ratio (OR) per 1-standard deviation increase in mean 2D:4D, 0.88 [95% confidence interval (CI) 0.65-1.21], p=0.435) or females (adjusted OR=1.36 [95% CI 0.81-2.28], p=0.245). Similar associations were observed after further adjustment for IQ. There was one weak association, discordant with the EMB theory, between reduced coherence and increased left 2D:4D in males (adjusted OR=1.15 [95% CI 1.02-1.29], p≤0.05). Given multiple comparisons, this may be consistent with chance.

Conclusions: In this population-based study, there was no association between 2D:4D and ASD diagnosis. There was weak, inconsistent evidence of association between 2D:4D and risk of ASD. These results are discordant with the extreme male brain theory of autism.