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The copy number variation and stroke (CaNVAS) risk and outcome study

Cole, John W ; Adigun, Taiwo ; Akinyemi, Rufus ; Akpa, Onoja Matthew ; Bell, Steven ; Chen, Bowang ; Conde, Jordi Jimenez ; Dobao, Uxue Lazcano ; Fernandez, Israel and Fornage, Myriam , et al. (2021) In PLoS ONE 16(4 April).
Abstract

Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and... (More)

Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
16
issue
4 April
article number
e0248791
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85104485683
  • pmid:33872305
ISSN
1932-6203
DOI
10.1371/journal.pone.0248791
language
English
LU publication?
yes
id
e23962eb-2be7-43a7-abe9-0f1590d89fe8
date added to LUP
2021-05-03 14:42:48
date last changed
2024-06-15 10:45:53
@article{e23962eb-2be7-43a7-abe9-0f1590d89fe8,
  abstract     = {{<p>Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.</p>}},
  author       = {{Cole, John W and Adigun, Taiwo and Akinyemi, Rufus and Akpa, Onoja Matthew and Bell, Steven and Chen, Bowang and Conde, Jordi Jimenez and Dobao, Uxue Lazcano and Fernandez, Israel and Fornage, Myriam and Gallego-Fabrega, Cristina and Jern, Christina and Krawczak, Michael and Lindgren, Arne and Markus, Hugh S. and Melander, Olle and Owolabi, Mayowa and Schlicht, Kristina and Söderholm, Martin and Srinivasasainagendra, Vinodh and Tárraga, Carolina Soriano and Stenman, Martin and Tiwari, Hemant and Corasaniti, Margaret and Fecteau, Natalie and Guizzardi, Beth and Lopez, Haley and Nguyen, Kevin and Gaynor, Brady and O’Connor, Timothy and Colin Stine, O. and Kittner, Steven J. and McArdle, Patrick and Mitchell, Braxton D. and Xu, Huichun and Grond-Ginsbach, Caspar}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{4 April}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{The copy number variation and stroke (CaNVAS) risk and outcome study}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0248791}},
  doi          = {{10.1371/journal.pone.0248791}},
  volume       = {{16}},
  year         = {{2021}},
}