Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods
In this study, the effects of (a) the minor allele frequency of the single nucleotide variant (SNV), (b) the degree of departure from normality of the trait, and (c) the position of the SNVs on type I error rates were investigated in the Genetic Analysis Workshop (GAW) 19 whole exome sequence data....
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BioMed Central
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133479/ |
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pubmed-51334792016-12-15 Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods Schwantes-An, Tae-Hwi Sung, Heejong Sabourin, Jeremy A. Justice, Cristina M. Sorant, Alexa J. M. Wilson, Alexander F. Proceedings In this study, the effects of (a) the minor allele frequency of the single nucleotide variant (SNV), (b) the degree of departure from normality of the trait, and (c) the position of the SNVs on type I error rates were investigated in the Genetic Analysis Workshop (GAW) 19 whole exome sequence data. To test the distribution of the type I error rate, 5 simulated traits were considered: standard normal and gamma distributed traits; 2 transformed versions of the gamma trait (log10 and rank-based inverse normal transformations); and trait Q1 provided by GAW 19. Each trait was tested with 313,340 SNVs. Tests of association were performed with simple linear regression and average type I error rates were determined for minor allele frequency classes. Rare SNVs (minor allele frequency < 0.05) showed inflated type I error rates for non–normally distributed traits that increased as the minor allele frequency decreased. The inflation of average type I error rates increased as the significance threshold decreased. Normally distributed traits did not show inflated type I error rates with respect to the minor allele frequency for rare SNVs. There was no consistent effect of transformation on the uniformity of the distribution of the location of SNVs with a type I error. BioMed Central 2016-10-18 /pmc/articles/PMC5133479/ /pubmed/27980666 http://dx.doi.org/10.1186/s12919-016-0060-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Schwantes-An, Tae-Hwi Sung, Heejong Sabourin, Jeremy A. Justice, Cristina M. Sorant, Alexa J. M. Wilson, Alexander F. |
| spellingShingle |
Schwantes-An, Tae-Hwi Sung, Heejong Sabourin, Jeremy A. Justice, Cristina M. Sorant, Alexa J. M. Wilson, Alexander F. Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| author_facet |
Schwantes-An, Tae-Hwi Sung, Heejong Sabourin, Jeremy A. Justice, Cristina M. Sorant, Alexa J. M. Wilson, Alexander F. |
| author_sort |
Schwantes-An, Tae-Hwi |
| title |
Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| title_short |
Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| title_full |
Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| title_fullStr |
Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| title_full_unstemmed |
Type I error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| title_sort |
type i error rates of rare single nucleotide variants are inflated in tests of association with non–normally distributed traits using simple linear regression methods |
| description |
In this study, the effects of (a) the minor allele frequency of the single nucleotide variant (SNV), (b) the degree of departure from normality of the trait, and (c) the position of the SNVs on type I error rates were investigated in the Genetic Analysis Workshop (GAW) 19 whole exome sequence data. To test the distribution of the type I error rate, 5 simulated traits were considered: standard normal and gamma distributed traits; 2 transformed versions of the gamma trait (log10 and rank-based inverse normal transformations); and trait Q1 provided by GAW 19. Each trait was tested with 313,340 SNVs. Tests of association were performed with simple linear regression and average type I error rates were determined for minor allele frequency classes. Rare SNVs (minor allele frequency < 0.05) showed inflated type I error rates for non–normally distributed traits that increased as the minor allele frequency decreased. The inflation of average type I error rates increased as the significance threshold decreased. Normally distributed traits did not show inflated type I error rates with respect to the minor allele frequency for rare SNVs. There was no consistent effect of transformation on the uniformity of the distribution of the location of SNVs with a type I error. |
| publisher |
BioMed Central |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133479/ |
| _version_ |
1613752464418275328 |