Multiple Significance Testing in Genetic Epidemiology

Michael Krawczak, Christian‐Albrechts‐Universität, Kiel, Germany

Published online: January 2006

DOI: 10.1038/npg.els.0005930

The simultaneous testing of multiple hypotheses in one and the same study tends to inflate the overall probability of obtaining one or more false positive results. Several methods have been devised to control this study-wise global false positive rate through the adjustment of the test-specific significance threshold applied to p-values. The necessity of adjusting the significance levels in genetic analyses of complex human traits has, however, been a matter of scientific debate.

Keywords: Bonferroni correction; linkage analysis; fine mapping; allelic association; LOD score

 References
    Bender R and Lange S (1999) Multiple test procedures other than Bonferroni's deserve wider use. British Medical Journal 318: 600–601.
    Boehringer S, Epplen JT and Krawczak M (2000) Genetic association studies of bronchial asthma – a need for Bonferroni correction? Human Genetics 107: 197.
    Camp NJ and Farnham JM (2001) Correcting for multiple analyses in genome-wide linkage studies. Annals of Human Genetics 65: 577–582.
    Holm S (1979) A simple sequentially rejective Bonferroni test procedure. Scandinavian Journal of Statistics 6: 65–70.
    Krawczak M, Boehringer S and Epplen JT (2001) Correcting for multiple testing in genetic association studies: the legend lives on. Human Genetics 109: 566–567.
    Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genetics 22: 139–144.
    Lander E and Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics 11: 241–247.
    Lin S, Rogers JA and Hsu JC (2001) A confidence-set approach for finding tightly linked genomic regions. American Journal of Human Genetics 68: 1219–1228.
    Morton NE (1955) Sequential tests for the detection of linkage. American Journal of Human Genetics 7: 277–318.
    Morton NE (1998) Significance levels in complex inheritance. American Journal of Human Genetics 62: 690–697.
    Perneger T (1998) What's wrong with Bonferroni adjustments? British Medical Journal 316: 1236–1238.
    Risch N and Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273: 1516–1517.
    Sawcer S, Jones HB, Judge D, et al. (1997) Empirical genome-wide significance levels established by whole genome simulations. Genetic Epidemiology 14: 223–229.
    Shaffer JP (1986) Modified sequentially rejective multiple test procedures. Journal of the American Statistical Association 81: 826–831.
    book Westfall PH and Young SS (1993) Resampling-based Multiple Testing. New York, NY: John Wiley.
    Witte JS, Elston RC and Schork N (1996) Genetic dissection of complex traits. Nature Genetics 12: 355–356.
    Zhao LP, Prentice R, Shen F and Hsu L (1999) On the assessment of statistical significance in disease-gene discovery. American Journal of Human Genetics 64: 1739–1753.
 Further Reading
    book Hochberg Y and Tamhane AC (1987) Multiple Comparisons Procedures New York, NY: John Wiley.
    book Hsu JC (1996) "Multiple Comparisons": Theory and Methods. London, UK: Chapman & Hall.
    book Ott J (1999) Analysis of Human Genetic Linkage Baltimore, MD: Johns Hopkins University Press.

Related Sub-Topics:

Linkage Analysis | Statistical Methodology in Genetics
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Multiple Significance Testing in Genetic Epidemiology
 
How to Cite close
Krawczak, Michael(Jan 2006) Multiple Significance Testing in Genetic Epidemiology. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005930]