No credible evidence for links between 2D:4D and COVID-19 outcomes: A probabilistic perspective on digit ratio, ACE variants, and national case fatalities

Early Hum Dev. 2021 Jan:152:105272. doi: 10.1016/j.earlhumdev.2020.105272. Epub 2020 Nov 17.

Abstract

Research into COVID-19 susceptibility and outcomes are critical, but claims must be carefully evaluated to inform policy decisions. In a recent series of articles, Manning and Fink [1-3] use national-level data to describe associations between case-fatality ratios and male and female finger ratios (2D:4D), a suggested measure of prenatal androgen exposure, as well as angiotensin-converting enzyme (ACE) allele and genotype frequencies. The authors suggest that 2D:4D is linked with ACE variant prevalence, and that higher male 2D:4D is associated with higher case fatality ratios, and point to 2D:4D as a useful prognostic measure for COVID-19 susceptibility. A critical review and robust Bayesian analysis of the hypothesis is described here, finding no conclusive evidence of COVID-19 mortality and 2D:4D, nor associations between 2D:4D and ACE1 allele or ACE2 genotype frequency. This absence of evidence is present for data taken from the second wave of COVID-19 in October 2020. Problematic theoretical grounding, individual-level conclusions drawn from national-level data, and issues with statistical inference in the original articles are discussed. Taken together, the current data offer no clear utility of 2D:4D in determining COVID-19 outcomes.

Keywords: 2D:4D; ACE; Bayesian inference; COVID-19; Digit ratio.

MeSH terms

  • Alleles
  • Anthropometry
  • COVID-19 / genetics
  • COVID-19 / mortality*
  • Female
  • Fingers*
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Prognosis

Substances

  • ACE protein, human
  • Peptidyl-Dipeptidase A