Cargando…

VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions

Copy number variations (CNVs) constitute a major source of genetic variations in human populations and have been reported to be associated with complex diseases. Methods have been developed for detecting CNVs and testing CNV associations in genome-wide association studies (GWAS) based on SNP arrays....

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Jianxin, Yang, Xiaohong R., Caporaso, Neil E., Landi, Maria T., Li, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957064/
https://www.ncbi.nlm.nih.gov/pubmed/24672538
http://dx.doi.org/10.3389/fgene.2014.00053
_version_ 1782307761759977472
author Shi, Jianxin
Yang, Xiaohong R.
Caporaso, Neil E.
Landi, Maria T.
Li, Peng
author_facet Shi, Jianxin
Yang, Xiaohong R.
Caporaso, Neil E.
Landi, Maria T.
Li, Peng
author_sort Shi, Jianxin
collection PubMed
description Copy number variations (CNVs) constitute a major source of genetic variations in human populations and have been reported to be associated with complex diseases. Methods have been developed for detecting CNVs and testing CNV associations in genome-wide association studies (GWAS) based on SNP arrays. Commonly used two-step testing procedures work well only for long CNVs while direct CNV association testing methods work only for recurrent CNVs. Assuming that short CNVs disrupting any part of a given genomic region increase disease risk, we developed a variable threshold exact test (VTET) for testing disease associations of CNVs randomly distributed in the genome using intensity data from SNP arrays. By extensive simulations, we found that VTET outperformed two-step testing procedures based on existing CNV calling algorithms for short CNVs and that the performance of VTET was robust to the length of the genomic region. In addition, VTET had a comparable performance with CNVtools for testing the association of recurrent CNVs. Thus, we expect VTET to be useful for testing disease associations of both recurrent and randomly distributed CNVs using existing GWAS data. We applied VTET to a lung cancer GWAS and identified a genome-wide significant region on chromosome 18q22.3 for lung squamous cell carcinoma.
format Online
Article
Text
id pubmed-3957064
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-39570642014-03-26 VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions Shi, Jianxin Yang, Xiaohong R. Caporaso, Neil E. Landi, Maria T. Li, Peng Front Genet Genetics Copy number variations (CNVs) constitute a major source of genetic variations in human populations and have been reported to be associated with complex diseases. Methods have been developed for detecting CNVs and testing CNV associations in genome-wide association studies (GWAS) based on SNP arrays. Commonly used two-step testing procedures work well only for long CNVs while direct CNV association testing methods work only for recurrent CNVs. Assuming that short CNVs disrupting any part of a given genomic region increase disease risk, we developed a variable threshold exact test (VTET) for testing disease associations of CNVs randomly distributed in the genome using intensity data from SNP arrays. By extensive simulations, we found that VTET outperformed two-step testing procedures based on existing CNV calling algorithms for short CNVs and that the performance of VTET was robust to the length of the genomic region. In addition, VTET had a comparable performance with CNVtools for testing the association of recurrent CNVs. Thus, we expect VTET to be useful for testing disease associations of both recurrent and randomly distributed CNVs using existing GWAS data. We applied VTET to a lung cancer GWAS and identified a genome-wide significant region on chromosome 18q22.3 for lung squamous cell carcinoma. Frontiers Media S.A. 2014-03-18 /pmc/articles/PMC3957064/ /pubmed/24672538 http://dx.doi.org/10.3389/fgene.2014.00053 Text en Copyright © 2014 Shi, Yang, Caporaso, Landi and Li. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Shi, Jianxin
Yang, Xiaohong R.
Caporaso, Neil E.
Landi, Maria T.
Li, Peng
VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title_full VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title_fullStr VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title_full_unstemmed VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title_short VTET: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
title_sort vtet: a variable threshold exact test for identifying disease-associated copy number variations enriched in short genomic regions
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957064/
https://www.ncbi.nlm.nih.gov/pubmed/24672538
http://dx.doi.org/10.3389/fgene.2014.00053
work_keys_str_mv AT shijianxin vtetavariablethresholdexacttestforidentifyingdiseaseassociatedcopynumbervariationsenrichedinshortgenomicregions
AT yangxiaohongr vtetavariablethresholdexacttestforidentifyingdiseaseassociatedcopynumbervariationsenrichedinshortgenomicregions
AT caporasoneile vtetavariablethresholdexacttestforidentifyingdiseaseassociatedcopynumbervariationsenrichedinshortgenomicregions
AT landimariat vtetavariablethresholdexacttestforidentifyingdiseaseassociatedcopynumbervariationsenrichedinshortgenomicregions
AT lipeng vtetavariablethresholdexacttestforidentifyingdiseaseassociatedcopynumbervariationsenrichedinshortgenomicregions