Strategy to Control Type I Error Increases Power to Identify Genetic Variation Using the Full Biological Trajectory

Genome‐wide association studies have been successful in identifying loci that underlie continuous traits measured at a single time point. To additionally consider continuous traits longitudinally, it is desirable to look at SNP effects at baseline and over time using linear‐mixed effects models. Est...

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Bibliographic Details
Published inGenetic epidemiology Vol. 37; no. 5; pp. 419 - 430
Main Authors Benke, K. S., Wu, Y., Fallin, D. M., Maher, B., Palmer, L. J.
Format Journal Article
LanguageEnglish
Published United States Blackwell Publishing Ltd 01.07.2013
Wiley Subscription Services, Inc
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Summary:Genome‐wide association studies have been successful in identifying loci that underlie continuous traits measured at a single time point. To additionally consider continuous traits longitudinally, it is desirable to look at SNP effects at baseline and over time using linear‐mixed effects models. Estimation and interpretation of two coefficients in the same model raises concern regarding the optimal control of type I error. To investigate this issue, we calculate type I error and power under an alternative for joint tests, including the two degree of freedom likelihood ratio test, and compare this to single degree of freedom tests for each effect separately at varying alpha levels. We show which joint tests are the optimal way to control the type I error and also illustrate that information can be gained by joint testing in situations where either or both SNP effects are underpowered. We also show that closed form power calculations can approximate simulated power for the case of balanced data, provide reasonable approximations for imbalanced data, but overestimate power for complicated residual error structures. We conclude that a two degree of freedom test is an attractive strategy in a hypothesis‐free genome‐wide setting and recommend its use for genome‐wide studies employing linear‐mixed effects models.
Bibliography:ark:/67375/WNG-W79VWDSS-R
istex:5852867A8DE058B67D6757B8DCC41397E05228F7
ArticleID:GEPI21733
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SourceType-Scholarly Journals-1
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content type line 23
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ISSN:0741-0395
1098-2272
DOI:10.1002/gepi.21733