Skip to main content
Log in

Variance estimation of allele-based odds ratio in the absence of Hardy–Weinberg equilibrium

  • METHODS
  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

In gene-disease association studies, deviation from Hardy–Weinberg equilibrium in controls may cause bias in estimating the allele-based estimates of genetic effects. An approach to adjust the variance of allele-based odds ratio for Hardy–Weinberg equilibrium deviation is proposed. Such adjustments have been introduced for estimating relative risks of genotype contrasts and differences in allele frequency; however, an adjustment of odds ratios for allele frequencies still does not exist. The approach was based on the delta method in combination with the Woolf’s logit interval method and the disequilibrium coefficient. The proposed variance adjustment provided better power than the unadjusted one to detect significant estimates of odds ratio and it improved the variance estimation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Zintzaras E, Koufakis T, Ziakas PD, Rodopoulou P, Giannouli S, Voulgarelis M. A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia. Eur J Epidemiol. 2006;21:501–10.

    Article  PubMed  CAS  Google Scholar 

  2. Weir BS. Genetic data analysis II: methods for discrete population genetic data. Sunderland, MA: Sinauer Associates; 1996.

    Google Scholar 

  3. Schaid DJ, Jacobsen SJ. Biased tests of association: comparisons of allele frequencies when departing from Hardy–Weinberg proportions. Am J Epidemiol. 1999;149:706–11.

    PubMed  CAS  Google Scholar 

  4. Zou GY, Donner A. The merits of testing Hardy–Weinberg equilibrium in the analysis of unmatched case–control data: a cautionary note. Ann Hum Genet. 2006;70:923–33.

    Article  PubMed  CAS  Google Scholar 

  5. Zintzaras E, Lau J. Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol. 2008. doi:10.1016/j.jclinepi.2007.12.011.

    Google Scholar 

  6. Sasieni PD. From genotypes to genes: doubling the sample size. Biometrics. 1997;53:1253–61.

    Article  PubMed  CAS  Google Scholar 

  7. Lathrop GM. Estimating genotype relative risks. Tissue Antigens. 1983;22:160–6.

    PubMed  CAS  Google Scholar 

  8. Agresti A. On logit confidence intervals for the odds ratio with small samples. Biometrics. 1999;55:597–602.

    Article  PubMed  CAS  Google Scholar 

  9. Silcocks P. An easy approach to the Robins–Breslow–Greenland variance estimator. Epidemiol Perspect Innov. 2005;2:1–6.

    Article  Google Scholar 

  10. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955;19:251–3.

    Article  PubMed  CAS  Google Scholar 

  11. Zintzaras E. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis. J Hum Genet. 2006;51:618–24.

    Article  PubMed  CAS  Google Scholar 

  12. Armitage P. Tests for linear trends in proportions and frequencies. Biometrics. 1955;11:375–86.

    Article  Google Scholar 

  13. Sato Y, Suganami H, Hamada C, Yoshimura I, Sakamoto H, Yoshida T, Yoshimura K. The confidence interval of allelic odds ratios under the Hardy–Weinberg disequilibrium. J Hum Genet. 2006;51:772–80.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elias Zintzaras.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zintzaras, E. Variance estimation of allele-based odds ratio in the absence of Hardy–Weinberg equilibrium. Eur J Epidemiol 23, 323–326 (2008). https://doi.org/10.1007/s10654-008-9242-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10654-008-9242-6

Keywords

Navigation