| Title: | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| Journal: | Nature Genetics |
| Published: | 15 Oct 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30323177/ |
| DOI: | https://doi.org/10.1038/s41588-018-0225-6 |
| URL: | https://ora.ox.ac.uk/objects/uuid:1eec35e5-0085-491a-9c93-1646553248f1/files/m7d748c28723379cc5d39341d1eb38eca |
Publication 7665
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Abstract
Identification of genetic variants with effects on trait variability can provide insights into the biological mechanisms that control variation and can identify potential interactions. We propose a two-degree-of-freedom test for jointly testing mean and variance effects to identify such variants. We implement the test in a linear mixed model, for which we provide an efficient algorithm and software. To focus on biologically interesting settings, we develop a test for dispersion effects, that is, variance effects not driven solely by mean effects when the trait distribution is non-normal. We apply our approach to body mass index in the subsample of the UK Biobank population with British ancestry (n ~408,000) and show that our approach can increase the power to detect associated loci. We identify and replicate novel associations with significant variance effects that cannot be explained by the non-normality of body mass index, and we provide suggestive evidence for a connection between leptin levels and body mass index variability.</p>
3 Authors
- Alexander I. Young
- Fabian L. Wauthier
- Peter Donnelly
Enabling scientific discoveries that improve human health