Journal of Autism and Developmental Disorders

, Volume 48, Issue 7, pp 2379–2395 | Cite as

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

  • Laura A. SchieveEmail author
  • Lin Tian
  • Nicole Dowling
  • Lisa Croen
  • Julie Hoover-Fong
  • Aimee Alexander
  • Stuart K. Shapira
Original Paper


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.


Autism spectrum disorder Testosterone Estradiol Fetal development 


Author Contributions

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.


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.

Compliance with Ethical Standards

Conflict of interest

All authors report no conflicts of interest for this study.

Ethical Approval

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.

Informed Consent

Informed consent was obtained from all participants in this study.


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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2018

Authors and Affiliations

  • Laura A. Schieve
    • 1
    Email author
  • Lin Tian
    • 1
  • Nicole Dowling
    • 1
  • Lisa Croen
    • 2
  • Julie Hoover-Fong
    • 3
  • Aimee Alexander
    • 1
  • Stuart K. Shapira
    • 1
  1. 1.National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionAtlantaUSA
  2. 2.Kaiser Permanente Division of ResearchOaklandUSA
  3. 3.McKusick-Nathans Institute of Genetic MedicineJohns Hopkins University School of MedicineBaltimoreUSA

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