The impact of a fine-scale population stratification on rare variant association test results.
Population stratification is a well-known confounding factor in both common and rare variant association analyses. Rare variants tend to be more geographically clustered than common variants, because of their more recent origin. However, it is not yet clear if population stratification at a very fin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0207677 |
| _version_ | 1818400207999598592 |
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| author | Elodie Persyn Richard Redon Lise Bellanger Christian Dina |
| author_facet | Elodie Persyn Richard Redon Lise Bellanger Christian Dina |
| author_sort | Elodie Persyn |
| collection | DOAJ |
| description | Population stratification is a well-known confounding factor in both common and rare variant association analyses. Rare variants tend to be more geographically clustered than common variants, because of their more recent origin. However, it is not yet clear if population stratification at a very fine scale (neighboring administrative regions within a country) would lead to statistical bias in rare variant analyses. As the inclusion of convenience controls from external studies is indeed a common procedure, in order to increase the power to detect genetic associations, this problem is important. We studied through simulation the impact of a fine scale population structure on different rare variant association strategies, assessing type I error and power. We showed that principal component analysis (PCA) based methods of adjustment for population stratification adequately corrected type I error inflation at the largest geographical scales, but not at finest scales. We also showed in our simulations that adding controls obviously increased power, but at a considerably lower level when controls were drawn from another population. |
| first_indexed | 2024-12-14T07:32:55Z |
| format | Article |
| id | doaj.art-cc76cbc10d404189ad9bf2be4d9883b8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T07:32:55Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cc76cbc10d404189ad9bf2be4d9883b82022-12-21T23:11:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020767710.1371/journal.pone.0207677The impact of a fine-scale population stratification on rare variant association test results.Elodie PersynRichard RedonLise BellangerChristian DinaPopulation stratification is a well-known confounding factor in both common and rare variant association analyses. Rare variants tend to be more geographically clustered than common variants, because of their more recent origin. However, it is not yet clear if population stratification at a very fine scale (neighboring administrative regions within a country) would lead to statistical bias in rare variant analyses. As the inclusion of convenience controls from external studies is indeed a common procedure, in order to increase the power to detect genetic associations, this problem is important. We studied through simulation the impact of a fine scale population structure on different rare variant association strategies, assessing type I error and power. We showed that principal component analysis (PCA) based methods of adjustment for population stratification adequately corrected type I error inflation at the largest geographical scales, but not at finest scales. We also showed in our simulations that adding controls obviously increased power, but at a considerably lower level when controls were drawn from another population.https://doi.org/10.1371/journal.pone.0207677 |
| spellingShingle | Elodie Persyn Richard Redon Lise Bellanger Christian Dina The impact of a fine-scale population stratification on rare variant association test results. PLoS ONE |
| title | The impact of a fine-scale population stratification on rare variant association test results. |
| title_full | The impact of a fine-scale population stratification on rare variant association test results. |
| title_fullStr | The impact of a fine-scale population stratification on rare variant association test results. |
| title_full_unstemmed | The impact of a fine-scale population stratification on rare variant association test results. |
| title_short | The impact of a fine-scale population stratification on rare variant association test results. |
| title_sort | impact of a fine scale population stratification on rare variant association test results |
| url | https://doi.org/10.1371/journal.pone.0207677 |
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