Genetic model misspecification in genetic association studies
Abstract Objective The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an error investigated previously. We explored this question, for candidate...
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doaj-db71a111105145ec8f6922976b93ee6b2020-11-25T01:58:42ZengBMCBMC Research Notes1756-05002017-11-011011610.1186/s13104-017-2911-3Genetic model misspecification in genetic association studiesAmadou Gaye0Sharon K. Davis1Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch, Social Epidemiology Research Unit, National Institutes of Health, National Human Genome Research InstituteMetabolic, Cardiovascular and Inflammatory Disease Genomics Branch, Social Epidemiology Research Unit, National Institutes of Health, National Human Genome Research InstituteAbstract Objective The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an error investigated previously. We explored this question, for candidate gene studies, by evaluating the sample size required to compensate for the misspecification and improve inference at the analysis stage. Power calculations were carried out with (1) the true dominant model and (2) the incorrect additive model. Empirical power, sample size and effect size were compared between scenarios (1) and (2). In each of the scenarios the estimates were evaluated for a rare (minor allele frequency < 0.01), low frequency (0.01 ≤ minor allele frequency < 0.05) and common (minor allele frequency ≥ 0.05) single nucleotide polymorphism. Results The results confirm the detrimental effect of the misspecification error on power and effect size for any minor allele frequency. The implications of the error are not negligible; therefore, candidate gene studies should consider the more conservative sample size to compensate for the effect of error. When it is not possible to extend the sample size, methods that help mitigate the impact of the error should be systematically used.http://link.springer.com/article/10.1186/s13104-017-2911-3Genetic association analysisIncorrect genetic modelStatistical power |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amadou Gaye Sharon K. Davis |
spellingShingle |
Amadou Gaye Sharon K. Davis Genetic model misspecification in genetic association studies BMC Research Notes Genetic association analysis Incorrect genetic model Statistical power |
author_facet |
Amadou Gaye Sharon K. Davis |
author_sort |
Amadou Gaye |
title |
Genetic model misspecification in genetic association studies |
title_short |
Genetic model misspecification in genetic association studies |
title_full |
Genetic model misspecification in genetic association studies |
title_fullStr |
Genetic model misspecification in genetic association studies |
title_full_unstemmed |
Genetic model misspecification in genetic association studies |
title_sort |
genetic model misspecification in genetic association studies |
publisher |
BMC |
series |
BMC Research Notes |
issn |
1756-0500 |
publishDate |
2017-11-01 |
description |
Abstract Objective The underlying model of the genetic determinant of a trait is generally not known with certainty a priori. Hence, in genetic association studies, a dominant model might be erroneously modelled as additive, an error investigated previously. We explored this question, for candidate gene studies, by evaluating the sample size required to compensate for the misspecification and improve inference at the analysis stage. Power calculations were carried out with (1) the true dominant model and (2) the incorrect additive model. Empirical power, sample size and effect size were compared between scenarios (1) and (2). In each of the scenarios the estimates were evaluated for a rare (minor allele frequency < 0.01), low frequency (0.01 ≤ minor allele frequency < 0.05) and common (minor allele frequency ≥ 0.05) single nucleotide polymorphism. Results The results confirm the detrimental effect of the misspecification error on power and effect size for any minor allele frequency. The implications of the error are not negligible; therefore, candidate gene studies should consider the more conservative sample size to compensate for the effect of error. When it is not possible to extend the sample size, methods that help mitigate the impact of the error should be systematically used. |
topic |
Genetic association analysis Incorrect genetic model Statistical power |
url |
http://link.springer.com/article/10.1186/s13104-017-2911-3 |
work_keys_str_mv |
AT amadougaye geneticmodelmisspecificationingeneticassociationstudies AT sharonkdavis geneticmodelmisspecificationingeneticassociationstudies |
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