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

Frontiers in Genetics

Neil eCaporaso¹  Maria Teresa Pia eLandi¹  Jianxin eShi¹  Xiaohong R. Yang¹  Peng eLi¹ 

[1] National Institute Of Health;

关键词: Genome-Wide Association Study;    Copy number varination;    variable threshold exact test;    Interval-based association test;    Lung cancer CNV analysis;   

DOI  :  10.3389/fgene.2014.00053

来源: DOAJ

【 摘 要 】

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. Assumingthat short CNVs disrupting any part of a given genomic region increase disease risk, wedeveloped 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.

【 授权许可】

Unknown