Hjem Publikasjoner Informed conditioning on clinical covaria[...]

Informed conditioning on clinical covariates increases power in case-control association studies

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  • 2012

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate...

Zaitlen, Noah; Lidström, Sara; Pasaniuc, Bogdan; Cornelis, Marilyn; Genovese, Giulio; Pollack, Samuela; Barton, Anne; Bickeböller, Heike; Bowden, Donald W.; Eyre, Steve; Freedman, Barry I.; Friedman, David J.; Field, John K.; Groop, Leif; Haugen, Aage; Heinrich, Joachim; Henderson, Brian E.; Hicks, Pamela J.; Hocking, Lynne J,; Kolonel, Laurence N.; Landi, Maria Teresa; Langefeld, Carl D.; Le Marchand, Loïc; Meister, Michael; Morgan, Ann W,; Raji, Olaide Y.; Risch, Angela; Rosenberger, Albert; Scherf, David; Steer, Sophia; Walshaw, Martin; Waters, Kevin M.; Wilson, Anthony G.; Wordsworth, Paul; Zienolddiny, Shanbeh; Tchetgen, Eric Tchetgen; Haiman, Cristopher; Hunter, David J.; Plenge, Robert M.; Worthington, Jane; Christiani, David C.; Schaumberg, Debra A.; Chasman, Daniel I.; Altshuler, David; Voight, Benjamin; Kraft, Peter; Patterson, Nick; Price, Alkes L
PLoS Genetics Public Library of Science (PLoS), PLoS Genetics 8(11)
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