Journal article
A robust mean and variance test with application to high-dimensional phenotypes
- Abstract:
- Most studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 2.4MB, Terms of use)
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- Publisher copy:
- 10.1007/s10654-021-00805-w
Authors
- Publisher:
- Springer
- Journal:
- European Journal of Epidemiology More from this journal
- Volume:
- 37
- Pages:
- 377–387
- Publication date:
- 2021-10-15
- Acceptance date:
- 2021-09-06
- DOI:
- EISSN:
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1573-7284
- ISSN:
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0393-2990
- Pmid:
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34651232
- Language:
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English
- Keywords:
- Pubs id:
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1205899
- Local pid:
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pubs:1205899
- Deposit date:
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2021-12-02
Terms of use
- Copyright holder:
- Staley et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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