Testing for an Unusual Distribution of Rare Variants
(2011) In PLoS Genetics 7(3).- Abstract
- Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants.... (More)
- Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1964828
- author
- Neale, Benjamin M. ; Rivas, Manuel A. ; Voight, Benjamin F. ; Altshuler, David ; Devlin, Bernie ; Orho-Melander, Marju LU ; Kathiresan, Sekar ; Purcell, Shaun M. ; Roeder, Kathryn and Daly, Mark J.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Genetics
- volume
- 7
- issue
- 3
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000288996600004
- scopus:79953752624
- ISSN
- 1553-7404
- DOI
- 10.1371/journal.pgen.1001322
- language
- English
- LU publication?
- yes
- id
- d5229f51-63cd-495a-9a1f-c37323d3f98c (old id 1964828)
- date added to LUP
- 2016-04-01 09:58:56
- date last changed
- 2025-04-04 14:35:21
@article{d5229f51-63cd-495a-9a1f-c37323d3f98c,
abstract = {{Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals.}},
author = {{Neale, Benjamin M. and Rivas, Manuel A. and Voight, Benjamin F. and Altshuler, David and Devlin, Bernie and Orho-Melander, Marju and Kathiresan, Sekar and Purcell, Shaun M. and Roeder, Kathryn and Daly, Mark J.}},
issn = {{1553-7404}},
language = {{eng}},
number = {{3}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Genetics}},
title = {{Testing for an Unusual Distribution of Rare Variants}},
url = {{http://dx.doi.org/10.1371/journal.pgen.1001322}},
doi = {{10.1371/journal.pgen.1001322}},
volume = {{7}},
year = {{2011}},
}