Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy

doi:10.21203/rs.3.rs-219649/v1

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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

https://doi.org/10.21203/rs.3.rs-219649/v1

This work is licensed under a CC BY 4.0 License

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posted 22 Feb, 2021

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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.

Epigenetics & Genomics

Chemotherapy-induced peripheral neuropathy (CIPN)

neuropathy

clinical trial

Taxanes

Single nucleotide polymorphisms (SNPs)

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Table 1: Merged dataset. List of most frequently sampled SNPs with frequency higher than 3%.

SNP	MeanC1	MeanC2	FR	Frequency
rs11880298_A	2.58	1.79	2.23	27.33
rs2779531_A	1.82	2.61	2.21	23.76
rs2163761_A	3.18	2.40	2.22	23.11
rs10978078_A	2.51	2.26	2.23	21.74
rs6930978_A	2.73	2.49	2.21	21.41
rs816318_A	3.18	2.46	2.21	20.03
rs4586191_A	2.53	1.79	2.22	18.09
rs3131529_A	2.75	2.50	2.25	17.19
rs7646392_A	2.31	2.59	2.18	16.38
rs2288778_A	1.87	2.56	2.17	15.73
rs6425872_A	1.87	2.59	2.18	15.17
rs6570180_A	3.13	2.42	2.18	14.76
rs7592247_A	2.29	2.56	2.19	14.11
rs4327389_A	1.69	1.41	2.17	13.22
rs5915412_A	2.29	2.51	2.17	12.57
rs7927376_A	3.13	2.47	2.17	12.17
rs11627891_A	3.69	3.47	2.14	9.98
rs12215647_A	1.93	2.62	2.15	9.49
rs6860447_A	3.07	2.39	2.14	9.49
rs775022_A	1.65	1.36	2.16	9.49
rs1984791_A	2.69	2.47	2.14	9.00
rs11072610_A	1.69	1.48	2.14	8.92
rs3006076_A	3.31	3.52	2.14	8.84
rs11968290_A	1.93	2.56	2.14	8.76
rs9472446_A	3.07	2.37	2.15	8.76
rs11079983_A	2.31	2.52	2.14	8.19
rs9830674_A	2.31	2.54	2.14	8.19
rs969768_A	2.31	2.55	2.15	8.11
rs7960673_A	2.69	2.47	2.14	7.95
rs6722224_A	1.31	1.54	2.14	7.87
rs12441544_A	1.93	2.64	2.15	7.79
rs756638_A	1.93	2.54	2.14	7.70
rs1893650_A	2.31	2.56	2.15	7.54
rs2829823_A	3.07	2.38	2.14	7.54
rs581753_A	1.93	2.60	2.14	7.38
rs1328452_A	2.60	2.32	2.16	7.06
rs4722598_A	2.31	2.51	2.14	7.06
rs9828652_A	3.69	3.49	2.14	7.06
rs6549465_A	2.69	2.49	2.14	6.81
rs10428343_A	3.29	3.56	2.12	6.65
rs11162463_A	2.20	3.03	2.15	6.24
rs892515_A	2.67	2.47	2.11	5.43
rs13216090_A	3.35	3.60	2.12	5.35
rs2352037_A	1.33	1.56	2.12	5.35
rs7593976_A	3.67	3.44	2.12	5.19
rs666930_A	2.44	2.70	2.16	5.03
rs11263806_A	1.98	2.59	2.11	4.95
rs17633749_A	3.02	2.32	2.12	4.95
rs1470121_A	3.02	2.41	2.11	4.79
rs251444_A	1.98	2.71	2.13	4.70
rs832164_A	1.98	2.58	2.11	4.70
rs1019153_A	3.02	2.39	2.11	4.62
rs10749134_A	1.98	2.61	2.11	4.62
rs7334528_A	3.02	2.43	2.11	4.62
rs4683236_A	2.04	2.83	2.14	4.54
rs1552186_A	1.51	1.29	2.18	4.38
rs4762693_A	1.98	2.58	2.11	4.38
rs7097501_A	1.98	2.61	2.11	4.38
rs3794346_A	2.67	2.47	2.11	4.30
rs6001762_A	2.67	2.44	2.12	4.30
rs9356970_A	1.98	2.57	2.10	4.22
rs10761507_A	1.33	1.56	2.12	4.14
rs1367211_A	3.02	2.42	2.11	4.14
rs2248273_A	1.98	2.71	2.13	4.14
rs4147672_A	1.98	2.53	2.11	4.14
rs4897517_A	2.33	2.52	2.11	4.14
rs6005101_A	2.33	2.51	2.11	4.14
rs9005_A	1.98	2.55	2.11	4.14
rs9373057_A	1.33	1.55	2.12	4.14
rs1596659_A	1.98	2.60	2.11	4.06
rs7216577_A	2.69	2.46	2.11	4.06
rs10857881_A	3.02	2.43	2.11	3.97
rs710887_A	1.98	2.56	2.11	3.97
rs1316479_A	2.51	2.29	2.18	3.89
rs1792738_A	2.67	2.49	2.11	3.89
rs5911269_A	2.67	2.45	2.12	3.89
rs7774664_A	1.98	2.54	2.11	3.89
rs4384353_A	2.33	2.52	2.11	3.81
rs12429505_A	2.67	2.49	2.11	3.73
rs16827937_A	3.02	2.35	2.12	3.73
rs270233_A	3.02	2.43	2.11	3.73
rs3993391_A	3.02	2.46	2.11	3.73
rs733299_A	3.67	3.48	2.11	3.73
rs3842990_A	1.98	2.65	2.12	3.65
rs6106303_A	2.04	2.77	2.12	3.65
rs7026988_A	2.55	2.30	2.16	3.57
rs1891659_A	1.98	2.55	2.11	3.49
rs2385826_A	1.98	2.55	2.11	3.49
rs207957_A	3.02	2.44	2.11	3.41
rs207958_A	3.02	2.44	2.11	3.41
rs1793426_A	1.98	2.52	2.11	3.33
rs7336083_A	3.02	2.42	2.11	3.33
rs7512417_A	1.98	2.55	2.11	3.33
rs1323881_A	1.98	2.54	2.11	3.24
rs11159741_A	2.35	2.58	2.11	3.16
rs17013665_A	2.33	2.51	2.11	3.16
rs2155803_A	2.33	2.50	2.11	3.16
rs12832515_A	1.98	2.54	2.11	3.00
rs3039_A	3.07	2.50	0.00	3.00

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Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy

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