Estimation of bias in nongenetic observational studies using "mendelian triangulation".

Annals of Epidemiology
L E BautistaJ P Casas

Abstract

Phenotype-disease odds ratios calculated from the effect of a genotype on its phenotype and on disease risk ("Mendelian triangulation") can be used as a standard to assess bias on the corresponding odds ratio from nongenetic studies. Statistical tests are commonly used to compare these odds ratios. We propose a method to estimate the magnitude of the bias and judge the validity of the phenotype-disease association. For four published examples, we obtained 10,000 random values from distributions of the odds ratios from both genetic and nongenetic studies. A range of values compatible with an unbiased odds ratio was then calculated from the empirical distribution of the differences between both odds ratios. We show that estimating a range of likely values for an unbiased odds ratio is useful to judge the effect of the phenotype and identify cases for which information from genetic studies adds little to the evaluation of the phenotype-disease association. Conversely, statistical tests could be misleading. Estimating a range of values for an unbiased odds ratio is more informative and appropriate than statistical tests when using the Mendelian triangulation approach for assessment of bias in phenotype-disease association studies.

References

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Citations

Mar 19, 2011·International Journal of Epidemiology·Stephen BurgessUNKNOWN CRP CHD Genetics Collaboration
Jan 11, 2011·Statistical Methods in Medical Research·Tom M PalmerJonathan A C Sterne
Nov 16, 2010·Human Genomics·Duncan C ThomasCornelia M Ulrich
Jun 12, 2013·PLoS Medicine·Irene PichlerCosetta Minelli
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
May 8, 2015·Statistics in Medicine·Fabiola Del Greco MJohn R Thompson
Apr 1, 2016·Journal of Alzheimer's Disease : JAD·Qingting HuNaidong Wang
Jun 28, 2016·International Journal of Epidemiology·Daniel I SwerdlowAroon D Hingorani
Aug 19, 2015·Statistical Methods in Medical Research·Stephen BurgessSimon G Thompson
Mar 28, 2006·International Journal of Epidemiology·Juan P CasasAroon D Hingorani
Mar 14, 2019·Neurology. Genetics·Neha S RaghavanRichard Mayeux
Oct 28, 2019·PLoS Genetics·Jenny C CensinCecilia M Lindgren

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