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Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development

Abstract

The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.

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Funding

This study was supported by six cooperative agreements from the Centers for Disease Control and Prevention: Cooperative Agreement Number U10DD000180, Colorado Department of Public Health; Cooperative Agreement Number U10DD000181, Kaiser Foundation Research Institute (CA); Cooperative Agreement Number U10DD000182, University of Pennsylvania; Cooperative Agreement Number U10DD000183, Johns Hopkins University; Cooperative Agreement Number U10DD000184, University of North Carolina at Chapel Hill; and Cooperative Agreement Number U10DD000498, Michigan State University.

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LAS made substantial contributions to acquisition of data, study conception and design, analysis and interpretation of data, drafting the article, revising the article critically for important intellectual content, and gave final approval of the version to be published. LT made substantial contributions to study conception and design, analysis and interpretation of data, revising the article critically for important intellectual content, and gave final approval of the version to be published. ND, LC, JH-F, AA and SKS made substantial contributions to acquisition of data, study conception and design, interpretation of data, revising the article critically for important intellectual content, and gave final approval of the version to be published.

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Correspondence to Laura A. Schieve.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all participants in this study.

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The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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Schieve, L.A., Tian, L., Dowling, N. et al. Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development. J Autism Dev Disord 48, 2379–2395 (2018). https://doi.org/10.1007/s10803-018-3495-z

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Keywords

  • Autism spectrum disorder
  • Testosterone
  • Estradiol
  • Fetal development