Identifying loci affecting trait variability and detecting interactions in genome-wide association studies
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...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2018
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| _version_ | 1797057383193640960 |
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| author | Young, A Wauthier, F Donnelly, P |
| author_facet | Young, A Wauthier, F Donnelly, P |
| author_sort | Young, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:35:32Z |
| format | Journal article |
| id | oxford-uuid:1eec35e5-0085-491a-9c93-1646553248f1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:35:32Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:1eec35e5-0085-491a-9c93-1646553248f12022-03-26T11:18:59ZIdentifying loci affecting trait variability and detecting interactions in genome-wide association studiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1eec35e5-0085-491a-9c93-1646553248f1EnglishSymplectic Elements at OxfordSpringer Nature2018Young, AWauthier, FDonnelly, PIdentification 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. |
| spellingShingle | Young, A Wauthier, F Donnelly, P Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title_full | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title_fullStr | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title_full_unstemmed | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title_short | Identifying loci affecting trait variability and detecting interactions in genome-wide association studies |
| title_sort | identifying loci affecting trait variability and detecting interactions in genome wide association studies |
| work_keys_str_mv | AT younga identifyinglociaffectingtraitvariabilityanddetectinginteractionsingenomewideassociationstudies AT wauthierf identifyinglociaffectingtraitvariabilityanddetectinginteractionsingenomewideassociationstudies AT donnellyp identifyinglociaffectingtraitvariabilityanddetectinginteractionsingenomewideassociationstudies |