A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

W. Meng (Lead / Corresponding author), H. A. Deshmukh, N. R. van Zuydam, Y. Liu, L. A. Donnelly, K. Zhou, Wellcome Trust Case Control Consortium 2 (WTCCC2), Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, A. D. Morris, H. M. Colhoun, C. N. A. Palmer, B. H. Smith

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    Abstract

    Background

    Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.
    Method

    We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.
    Results

    After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10−7 at rs17428041. The narrow-sense heritability of this phenotype was 11.00%.
    Conclusion

    This genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.
    Original languageEnglish
    Pages (from-to)392-399
    Number of pages8
    JournalEuropean Journal of Pain
    Volume19
    Issue number3
    Early online date26 Jun 2014
    DOIs
    Publication statusPublished - Mar 2015

    Fingerprint

    Genome-Wide Association Study
    Neuralgia
    Prescriptions
    Pain
    Diabetes Complications
    Opioid Analgesics
    Single Nucleotide Polymorphism
    Genotype
    Genome
    Phenotype
    Research
    Pharmaceutical Preparations
    Population
    Datasets
    Therapeutics

    Cite this

    Meng, W. ; Deshmukh, H. A. ; van Zuydam, N. R. ; Liu, Y. ; Donnelly, L. A. ; Zhou, K. ; Wellcome Trust Case Control Consortium 2 (WTCCC2) ; Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group ; Morris, A. D. ; Colhoun, H. M. ; Palmer, C. N. A. ; Smith, B. H. / A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain. In: European Journal of Pain. 2015 ; Vol. 19, No. 3. pp. 392-399.
    @article{d17bd057c35a4bcca17255df1525d84d,
    title = "A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain",
    abstract = "BackgroundNeuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.MethodWe accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.ResultsAfter data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10−7 at rs17428041. The narrow-sense heritability of this phenotype was 11.00{\%}.ConclusionThis genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.",
    author = "W. Meng and Deshmukh, {H. A.} and {van Zuydam}, {N. R.} and Y. Liu and Donnelly, {L. A.} and K. Zhou and {Wellcome Trust Case Control Consortium 2 (WTCCC2)} and {Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group} and Morris, {A. D.} and Colhoun, {H. M.} and Palmer, {C. N. A.} and Smith, {B. H.}",
    note = "{\circledC} 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC{\circledR}.",
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    Meng, W, Deshmukh, HA, van Zuydam, NR, Liu, Y, Donnelly, LA, Zhou, K, Wellcome Trust Case Control Consortium 2 (WTCCC2), Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, Morris, AD, Colhoun, HM, Palmer, CNA & Smith, BH 2015, 'A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain', European Journal of Pain, vol. 19, no. 3, pp. 392-399. https://doi.org/10.1002/ejp.560

    A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain. / Meng, W. (Lead / Corresponding author); Deshmukh, H. A.; van Zuydam, N. R.; Liu, Y.; Donnelly, L. A.; Zhou, K.; Wellcome Trust Case Control Consortium 2 (WTCCC2); Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group; Morris, A. D.; Colhoun, H. M.; Palmer, C. N. A.; Smith, B. H.

    In: European Journal of Pain, Vol. 19, No. 3, 03.2015, p. 392-399.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

    AU - Meng, W.

    AU - Deshmukh, H. A.

    AU - van Zuydam, N. R.

    AU - Liu, Y.

    AU - Donnelly, L. A.

    AU - Zhou, K.

    AU - Wellcome Trust Case Control Consortium 2 (WTCCC2)

    AU - Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group

    AU - Morris, A. D.

    AU - Colhoun, H. M.

    AU - Palmer, C. N. A.

    AU - Smith, B. H.

    N1 - © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

    PY - 2015/3

    Y1 - 2015/3

    N2 - BackgroundNeuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.MethodWe accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.ResultsAfter data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10−7 at rs17428041. The narrow-sense heritability of this phenotype was 11.00%.ConclusionThis genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.

    AB - BackgroundNeuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population.MethodWe accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non-genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets.ResultsAfter data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p-value of 1.77 × 10−7 at rs17428041. The narrow-sense heritability of this phenotype was 11.00%.ConclusionThis genome-wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level.

    U2 - 10.1002/ejp.560

    DO - 10.1002/ejp.560

    M3 - Article

    VL - 19

    SP - 392

    EP - 399

    JO - European Journal of Pain

    JF - European Journal of Pain

    SN - 1090-3801

    IS - 3

    ER -