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A genome‐wide association study suggests an association of C hr8p21.3 ( GFRA2 ) with diabetic neuropathic pain
Author(s) -
Meng W.,
Deshmukh H.A.,
Zuydam N.R.,
Liu Y.,
Donnelly L.A.,
Zhou K.,
Morris A.D.,
Colhoun H.M.,
Palmer C.N.A.,
Smith B.H.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.560
Subject(s) - neuropathic pain , medicine , diabetes mellitus , diabetic neuropathy , population , genome wide association study , single nucleotide polymorphism , neuralgia , diabetic foot , anesthesia , genotype , endocrinology , genetics , environmental health , biology , gene
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 G enetics of D iabetes A udit and R esearch T ayside ( GoDARTS ) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by A ffymetrix SNP 6.0 or I llumina O mni E xpress 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 IMPUTE 2, with reference files from 1000 G enomes P hase 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 C hr8p21.3, 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.