A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain

Weihua Meng; Harshal A. Deshmukh; Louise A. Donnelly; Wellcome Trust Case Control Consortium 2; Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group; Nicola Torrance; Helen M. Colhoun; Colin N. A. Palmer; Blair H. Smith

doi:10.1016/j.ebiom.2015.08.001

A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain

Weihua Meng (Lead / Corresponding author), Harshal A. Deshmukh, Louise A. Donnelly, Wellcome Trust Case Control Consortium 2, Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, Nicola Torrance, Helen M. Colhoun, Colin N. A. Palmer, Blair H. Smith

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Abstract

Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS) was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS) cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P) with a lowest P value of 2.74 × 10⁻⁷ at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10⁻⁷ at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0%) than in females (14.7%). This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with the disorder, indicating the need for further research.

Original language	English
Pages (from-to)	1386-1393
Number of pages	8
Journal	EBioMedicine
Volume	2
Issue number	10
Early online date	4 Aug 2015
DOIs	https://doi.org/10.1016/j.ebiom.2015.08.001
Publication status	Published - Oct 2015

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© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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http://www.sciencedirect.com/science/article/pii/S2352396415300955

Meng, Weihua
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Meng, W., Deshmukh, H. A., Donnelly, L. A., Wellcome Trust Case Control Consortium 2, Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, Torrance, N., Colhoun, H. M., Palmer, C. N. A., & Smith, B. H. (2015). A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain. EBioMedicine, 2(10), 1386-1393. https://doi.org/10.1016/j.ebiom.2015.08.001

@article{8034745964fe4f9886532ca673168ec4,

title = "A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain",

abstract = "Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS) was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS) cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P) with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0%) than in females (14.7%). This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with the disorder, indicating the need for further research.",

author = "Weihua Meng and Deshmukh, {Harshal A.} and Donnelly, {Louise A.} and {Wellcome Trust Case Control Consortium 2} and {Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group} and Nicola Torrance and Colhoun, {Helen M.} and Palmer, {Colin N. A.} and Smith, {Blair H.}",

year = "2015",

month = oct,

doi = "10.1016/j.ebiom.2015.08.001",

language = "English",

volume = "2",

pages = "1386--1393",

journal = "EBioMedicine",

publisher = "Elsevier",

number = "10",

}

Meng, W, Deshmukh, HA, Donnelly, LA, Wellcome Trust Case Control Consortium 2, Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, Torrance, N, Colhoun, HM, Palmer, CNA & Smith, BH 2015, 'A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain', EBioMedicine, vol. 2, no. 10, pp. 1386-1393. https://doi.org/10.1016/j.ebiom.2015.08.001

A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain. / Meng, Weihua (Lead / Corresponding author); Deshmukh, Harshal A.; Donnelly, Louise A. et al.
In: EBioMedicine, Vol. 2, No. 10, 10.2015, p. 1386-1393.

Research output: Contribution to journal › Article › peer-review

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T1 - A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain

AU - Meng, Weihua

AU - Deshmukh, Harshal A.

AU - Donnelly, Louise A.

AU - Wellcome Trust Case Control Consortium 2

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

AU - Torrance, Nicola

AU - Colhoun, Helen M.

AU - Palmer, Colin N. A.

AU - Smith, Blair H.

PY - 2015/10

Y1 - 2015/10

N2 - Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS) was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS) cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P) with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0%) than in females (14.7%). This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with the disorder, indicating the need for further research.

AB - Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS) was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS) cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P) with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0%) than in females (14.7%). This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with the disorder, indicating the need for further research.

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Meng W, Deshmukh HA, Donnelly LA, Wellcome Trust Case Control Consortium 2, Surrogate Markers for Micro- and Macro-Vascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) Study Group, Torrance N et al. A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain. EBioMedicine. 2015 Oct;2(10):1386-1393. Epub 2015 Aug 4. doi: 10.1016/j.ebiom.2015.08.001

A genome-wide association study provides evidence of sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with diabetic neuropathic pain

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