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Research article
Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy
Maryam Lustberg
Ohio State University School of Medicine
Corresponding Author
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Background
Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytic to describe taxane-associated CIPN risk.
Methods
We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher’s ratio. We then ranked ordered those SNPs which discriminated CIPN-positive from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross validation (LOOCV).
Results
Using GWAS aggregate data, we identified a 267 SNP cluster which was associated with a CIPN+ phenotype with an accuracy of 96.1%.
Conclusions
Identification of a 267 SNP cluster could accurately predict CIPN risk. Validation using an independent patient cohort should be performed.
Keywords
Chemotherapy-induced peripheral neuropathy (CIPN), neuropathy, clinical trial, Taxanes, Single nucleotide polymorphisms (SNPs)
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Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Feb, 2021
No community comments so far
Reviewer #1 agreed
On 08 Feb, 2021
Review #1 received
Received 08 Feb, 2021
Reviewers invited
Invitations sent on 07 Feb, 2021
Editor assigned
On 03 Feb, 2021
Submission checks complete
On 03 Feb, 2021
Editor invited
On 03 Feb, 2021
First submitted
On 31 Jan, 2021
Metrics
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HTML Views: ...
Subject Areas
Epigenetics & Genomics
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This preprint is under consideration at BMC Medical Genomics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy
Maryam Lustberg
Ohio State University School of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Feb, 2021
No community comments so far
Reviewer #1 agreed
On 08 Feb, 2021
Review #1 received
Received 08 Feb, 2021
Reviewers invited
Invitations sent on 07 Feb, 2021
Editor assigned
On 03 Feb, 2021
Submission checks complete
On 03 Feb, 2021
Editor invited
On 03 Feb, 2021
First submitted
On 31 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytic to describe taxane-associated CIPN risk.
Methods
We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher’s ratio. We then ranked ordered those SNPs which discriminated CIPN-positive from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross validation (LOOCV).
Results
Using GWAS aggregate data, we identified a 267 SNP cluster which was associated with a CIPN+ phenotype with an accuracy of 96.1%.
Conclusions
Identification of a 267 SNP cluster could accurately predict CIPN risk. Validation using an independent patient cohort should be performed.
Figure 1
Figure 2
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF.