Dataset Information

Validity of using ad hoc methods to analyze secondary traits in case-control association studies.

ABSTRACT: Case-control association studies often collect from their subjects information on secondary phenotypes. Reusing the data and studying the association between genes and secondary phenotypes provide an attractive and cost-effective approach that can lead to discovery of new genetic associations. A number of approaches have been proposed, including simple and computationally efficient ad hoc methods that ignore ascertainment or stratify on case-control status. Justification for these approaches relies on the assumption of no covariates and the correct specification of the primary disease model as a logistic model. Both might not be true in practice, for example, in the presence of population stratification or the primary disease model following a probit model. In this paper, we investigate the validity of ad hoc methods in the presence of covariates and possible disease model misspecification. We show that in taking an ad hoc approach, it may be desirable to include covariates that affect the primary disease in the secondary phenotype model, even though these covariates are not necessarily associated with the secondary phenotype. We also show that when the disease is rare, ad hoc methods can lead to severely biased estimation and inference if the true disease model follows a probit model instead of a logistic model. Our results are justified theoretically and via simulations. Applied to real data analysis of genetic associations with cigarette smoking, ad hoc methods collectively identified as highly significant (P<10-5) single nucleotide polymorphisms from over 10 genes, genes that were identified in previous studies of smoking cessation.

SUBMITTER: Yung G

PROVIDER: S-EPMC5170877 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Validity of using ad hoc methods to analyze secondary traits in case-control association studies.

Yung Godwin G Lin Xihong X

Genetic epidemiology 20160926 8

Case-control association studies often collect from their subjects information on secondary phenotypes. Reusing the data and studying the association between genes and secondary phenotypes provide an attractive and cost-effective approach that can lead to discovery of new genetic associations. A number of approaches have been proposed, including simple and computationally efficient ad hoc methods that ignore ascertainment or stratify on case-control status. Justification for these approaches rel ...[more]

PMID: 27670932

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Project description:In light of global climate change, ecological studies increasingly address effects of temperature on organisms and ecosystems. To measure air temperature at biologically relevant scales in the field, ecologists often use small, portable temperature sensors. Sensors must be shielded from solar radiation to provide accurate temperature measurements, but our review of 18 years of ecological literature indicates that shielding practices vary across studies (when reported at all), and that ecologists often invent and construct ad hoc radiation shields without testing their efficacy. We performed two field experiments to examine the accuracy of temperature observations from three commonly used portable data loggers (HOBO Pro, HOBO Pendant, and iButton hygrochron) housed in manufactured Gill shields or ad hoc, custom-fabricated shields constructed from everyday materials such as plastic cups. We installed this sensor array (five replicates of 11 sensor-shield combinations) at weather stations located in open and forested sites. HOBO Pro sensors with Gill shields were the most accurate devices, with a mean absolute error of 0.2°C relative to weather stations at each site. Error in ad hoc shield treatments ranged from 0.8 to 3.0°C, with the largest errors at the open site. We then deployed one replicate of each sensor-shield combination at five sites that varied in the amount of urban impervious surface cover, which presents a further shielding challenge. Bias in sensors paired with ad hoc shields increased by up to 0.7°C for every 10% increase in impervious surface. Our results indicate that, due to variable shielding practices, the ecological literature likely includes highly biased temperature data that cannot be compared directly across studies. If left unaddressed, these errors will hinder efforts to predict biological responses to climate change. We call for greater standardization in how temperature data are recorded in the field, handled in analyses, and reported in publications.

Dataset Information

Validity of using ad hoc methods to analyze secondary traits in case-control association studies.

Publications

Validity of using ad hoc methods to analyze secondary traits in case-control association studies.

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