Association Testing of Clustered Rare Causal Variants in Case-Control Studies
Biological evidence suggests that multiple causal variants in a gene may cluster physically. Variants within the same protein functional domain or gene regulatory element would locate in close proximity on the DNA sequence. However, spatial information of variants is usually not used in current rare...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988195/ |
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pubmed-3988195 |
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pubmed-39881952014-04-21 Association Testing of Clustered Rare Causal Variants in Case-Control Studies Lin, Wan-Yu Research Article Biological evidence suggests that multiple causal variants in a gene may cluster physically. Variants within the same protein functional domain or gene regulatory element would locate in close proximity on the DNA sequence. However, spatial information of variants is usually not used in current rare variant association analyses. We here propose a clustering method (abbreviated as “CLUSTER”), which is extended from the adaptive combination of P-values. Our method combines the association signals of variants that are more likely to be causal. Furthermore, the statistic incorporates the spatial information of variants. With extensive simulations, we show that our method outperforms several commonly-used methods in many scenarios. To demonstrate its use in real data analyses, we also apply this CLUSTER test to the Dallas Heart Study data. CLUSTER is among the best methods when the effects of causal variants are all in the same direction. As variants located in close proximity are more likely to have similar impact on disease risk, CLUSTER is recommended for association testing of clustered rare causal variants in case-control studies. Public Library of Science 2014-04-15 /pmc/articles/PMC3988195/ /pubmed/24736372 http://dx.doi.org/10.1371/journal.pone.0094337 Text en © 2014 Wan-Yu Lin http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lin, Wan-Yu |
| spellingShingle |
Lin, Wan-Yu Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| author_facet |
Lin, Wan-Yu |
| author_sort |
Lin, Wan-Yu |
| title |
Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| title_short |
Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| title_full |
Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| title_fullStr |
Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| title_full_unstemmed |
Association Testing of Clustered Rare Causal Variants in Case-Control Studies |
| title_sort |
association testing of clustered rare causal variants in case-control studies |
| description |
Biological evidence suggests that multiple causal variants in a gene may cluster physically. Variants within the same protein functional domain or gene regulatory element would locate in close proximity on the DNA sequence. However, spatial information of variants is usually not used in current rare variant association analyses. We here propose a clustering method (abbreviated as “CLUSTER”), which is extended from the adaptive combination of P-values. Our method combines the association signals of variants that are more likely to be causal. Furthermore, the statistic incorporates the spatial information of variants. With extensive simulations, we show that our method outperforms several commonly-used methods in many scenarios. To demonstrate its use in real data analyses, we also apply this CLUSTER test to the Dallas Heart Study data. CLUSTER is among the best methods when the effects of causal variants are all in the same direction. As variants located in close proximity are more likely to have similar impact on disease risk, CLUSTER is recommended for association testing of clustered rare causal variants in case-control studies. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988195/ |
| _version_ |
1612078661865832448 |