Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context.
Assessment of the genetic similarity between two phenotypes can provide insight into a common genetic aetiology and inform the use of pleiotropy-informed, cross-phenotype analytical methods to identify novel genetic associations. The genetic correlation is a well-known means of quantifying and testi...
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Public Library of Science (PLoS)
2023-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010852&type=printable |
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| author | Thomas W Willis Chris Wallace |
| author_facet | Thomas W Willis Chris Wallace |
| author_sort | Thomas W Willis |
| collection | DOAJ |
| description | Assessment of the genetic similarity between two phenotypes can provide insight into a common genetic aetiology and inform the use of pleiotropy-informed, cross-phenotype analytical methods to identify novel genetic associations. The genetic correlation is a well-known means of quantifying and testing for genetic similarity between traits, but its estimates are subject to comparatively large sampling error. This makes it unsuitable for use in a small-sample context. We discuss the use of a previously published nonparametric test of genetic similarity for application to GWAS summary statistics. We establish that the null distribution of the test statistic is modelled better by an extreme value distribution than a transformation of the standard exponential distribution. We show with simulation studies and real data from GWAS of 18 phenotypes from the UK Biobank that the test is to be preferred for use with small sample sizes, particularly when genetic effects are few and large, outperforming the genetic correlation and another nonparametric statistical test of independence. We find the test suitable for the detection of genetic similarity in the rare disease context. |
| format | Article |
| id | doaj-art-e94b4583e90b444797c6542aee320ef4 |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2023-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e94b4583e90b444797c6542aee320ef42025-08-20T03:25:19ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-08-01198e101085210.1371/journal.pgen.1010852Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context.Thomas W WillisChris WallaceAssessment of the genetic similarity between two phenotypes can provide insight into a common genetic aetiology and inform the use of pleiotropy-informed, cross-phenotype analytical methods to identify novel genetic associations. The genetic correlation is a well-known means of quantifying and testing for genetic similarity between traits, but its estimates are subject to comparatively large sampling error. This makes it unsuitable for use in a small-sample context. We discuss the use of a previously published nonparametric test of genetic similarity for application to GWAS summary statistics. We establish that the null distribution of the test statistic is modelled better by an extreme value distribution than a transformation of the standard exponential distribution. We show with simulation studies and real data from GWAS of 18 phenotypes from the UK Biobank that the test is to be preferred for use with small sample sizes, particularly when genetic effects are few and large, outperforming the genetic correlation and another nonparametric statistical test of independence. We find the test suitable for the detection of genetic similarity in the rare disease context.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010852&type=printable |
| spellingShingle | Thomas W Willis Chris Wallace Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. PLoS Genetics |
| title | Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. |
| title_full | Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. |
| title_fullStr | Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. |
| title_full_unstemmed | Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. |
| title_short | Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context. |
| title_sort | accurate detection of shared genetic architecture from gwas summary statistics in the small sample context |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010852&type=printable |
| work_keys_str_mv | AT thomaswwillis accuratedetectionofsharedgeneticarchitecturefromgwassummarystatisticsinthesmallsamplecontext AT chriswallace accuratedetectionofsharedgeneticarchitecturefromgwassummarystatisticsinthesmallsamplecontext |