Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy
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.
This is a list of supplementary files associated with this preprint. Click to download.
Posted 22 Feb, 2021
On 08 Feb, 2021
Received 08 Feb, 2021
Invitations sent on 07 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 31 Jan, 2021
Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy
Posted 22 Feb, 2021
On 08 Feb, 2021
Received 08 Feb, 2021
Invitations sent on 07 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 31 Jan, 2021
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.