A novel copy number variants kernel association test with application to autism spectrum disorders studies

Xiang Zhan, Santhosh Girirajan, Ni Zhao, Michael C. Wu, Debashis Ghosh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Motivation: Copy number variants (CNVs) have been implicated in a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability and schizophrenia. Recent advances in high-throughput genomic technologies have enabled rapid discovery of many genetic variants including CNVs. As a result, there is increasing interest in studying the role of CNVs in the etiology of many complex diseases. Despite the availability of an unprecedented wealth of CNV data, methods for testing association between CNVs and disease-related traits are still underdeveloped due to the low prevalence and complicated multi-scale features of CNVs. Results: We propose a novel CNV kernel association test (CKAT) in this paper. To address the low prevalence, CNVs are first grouped into CNV regions (CNVR). Then, taking into account the multiscale features of CNVs, we first design a single-CNV kernel which summarizes the similarity between two CNVs, and next aggregate the single-CNV kernel to a CNVR kernel which summarizes the similarity between two CNVRs. Finally, association between CNVR and disease-related traits is assessed by comparing the kernel-based similarity with the similarity in the trait using a score test for variance components in a random effect model.We illustrate the proposed CKAT using simulations and show that CKAT is more powerful than existing methods, while always being able to control the type I error. We also apply CKAT to a real dataset examining the association between CNV and autism spectrum disorders, which demonstrates the potential usefulness of the proposed method.

Original languageEnglish (US)
Pages (from-to)3603-3610
Number of pages8
JournalBioinformatics
Volume32
Issue number23
DOIs
StatePublished - Jan 1 2016

Fingerprint

Disorder
kernel
Intellectual Disability
Schizophrenia
Throughput
Availability
Technology
Testing
Autism Spectrum Disorder
Variance Components
Type I error
Random Effects Model
Score Test
Disability
High Throughput
Genomics
Neurodevelopmental Disorders
Datasets

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

Cite this

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title = "A novel copy number variants kernel association test with application to autism spectrum disorders studies",
abstract = "Motivation: Copy number variants (CNVs) have been implicated in a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability and schizophrenia. Recent advances in high-throughput genomic technologies have enabled rapid discovery of many genetic variants including CNVs. As a result, there is increasing interest in studying the role of CNVs in the etiology of many complex diseases. Despite the availability of an unprecedented wealth of CNV data, methods for testing association between CNVs and disease-related traits are still underdeveloped due to the low prevalence and complicated multi-scale features of CNVs. Results: We propose a novel CNV kernel association test (CKAT) in this paper. To address the low prevalence, CNVs are first grouped into CNV regions (CNVR). Then, taking into account the multiscale features of CNVs, we first design a single-CNV kernel which summarizes the similarity between two CNVs, and next aggregate the single-CNV kernel to a CNVR kernel which summarizes the similarity between two CNVRs. Finally, association between CNVR and disease-related traits is assessed by comparing the kernel-based similarity with the similarity in the trait using a score test for variance components in a random effect model.We illustrate the proposed CKAT using simulations and show that CKAT is more powerful than existing methods, while always being able to control the type I error. We also apply CKAT to a real dataset examining the association between CNV and autism spectrum disorders, which demonstrates the potential usefulness of the proposed method.",
author = "Xiang Zhan and Santhosh Girirajan and Ni Zhao and Wu, {Michael C.} and Debashis Ghosh",
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A novel copy number variants kernel association test with application to autism spectrum disorders studies. / Zhan, Xiang; Girirajan, Santhosh; Zhao, Ni; Wu, Michael C.; Ghosh, Debashis.

In: Bioinformatics, Vol. 32, No. 23, 01.01.2016, p. 3603-3610.

Research output: Contribution to journalArticle

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