A Robust Statistical Method for Case-control Association Testing with Copy Number Variation

Overview

Journal Nat Genet

Specialty Genetics

Date 2008 Sep 9

PMID 18776912

Citations 98

Authors

Chris Barnes

Vincent Plagnol

Tomas Fitzgerald

Richard Redon

Jonathan Marchini

David Clayton

Matthew E Hurles

Affiliations

Soon will be listed here.

Abstract

Copy number variation (CNV) is pervasive in the human genome and can play a causal role in genetic diseases. The functional impact of CNV cannot be fully captured through linkage disequilibrium with SNPs. These observations motivate the development of statistical methods for performing direct CNV association studies. We show through simulation that current tests for CNV association are prone to false-positive associations in the presence of differential errors between cases and controls, especially if quantitative CNV measurements are noisy. We present a statistical framework for performing case-control CNV association studies that applies likelihood ratio testing of quantitative CNV measurements in cases and controls. We show that our methods are robust to differential errors and noisy data and can achieve maximal theoretical power. We illustrate the power of these methods for testing for association with binary and quantitative traits, and have made this software available as the R package CNVtools.

Citing Articles

Genetic Association Analysis of Copy Number Variations for Meat Quality in Beef Cattle.

Wu J, Wu T, Xie X, Niu Q, Zhao Z, Zhu B Foods. 2023; 12(21).

PMID: 37959106 PMC: 10647706. DOI: 10.3390/foods12213986.

A Novel Computational Framework to Predict Disease-Related Copy Number Variations by Integrating Multiple Data Sources.

Yuan L, Sun T, Zhao J, Shen Z Front Genet. 2021; 12:696956.

PMID: 34267783 PMC: 8276077. DOI: 10.3389/fgene.2021.696956.

A novel synonymous variant in exon 1 of gene results in a cryptic splice site and causes pseudohypoparathyroidism type 1A and pseudo-pseudohypoparathyroidism in a French family.

Apetrei A, Molin A, Gruchy N, Godin M, Bracquemart C, Resbeut A Bone Rep. 2021; 14:101073.

PMID: 33997150 PMC: 8100090. DOI: 10.1016/j.bonr.2021.101073.

MADloy: robust detection of mosaic loss of chromosome Y from genotype-array-intensity data.

Gonzalez J, Lopez-Sanchez M, Caceres A, Puig P, Esko T, Perez-Jurado L BMC Bioinformatics. 2020; 21(1):533.

PMID: 33225898 PMC: 7682048. DOI: 10.1186/s12859-020-03768-z.

Detecting rare copy number variants from Illumina genotyping arrays with the CamCNV pipeline: Segmentation of z-scores improves detection and reliability.

Dennis J, Walker L, Tyrer J, Michailidou K, Easton D Genet Epidemiol. 2020; 45(3):237-248.

PMID: 33020983 PMC: 8005414. DOI: 10.1002/gepi.22367.

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