Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort.

Journal

Pain

ISSN: 1872-6623

Titre abrégé: Pain

Pays: United States

ID NLM: 7508686

Informations de publication

Date de publication:
29 Oct 2024

Historique:

received: 08 05 2024

accepted: 27 09 2024

medline: 29 10 2024

pubmed: 29 10 2024

entrez: 29 10 2024

Statut: aheadofprint

Résumé

We aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10-8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the "irritable" nociceptor profile to those with a "nonirritable" nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10-8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.

Identifiants

DOI: 10.1097/j.pain.0000000000003463 PMID: 39471050

pubmed: 39471050

doi: 10.1097/j.pain.0000000000003463

pii: 00006396-990000000-00756

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Wellcome Trust

ID : 223149/Z/21/Z

Pays : United Kingdom

Organisme : Medical Research Council

ID : MR/T020113/1

Pays : United Kingdom

Organisme : H2020 European Institute of Innovation and Technology

ID : No 633491

Organisme : Novo Nordisk

ID : NNF14OC0011633

Organisme : Eli Lilly and Company

ID : MR/W002388/1

Organisme : Norwegian Research Council

ID : 275476

Organisme : European Commission

ID : 2013-602891

Organisme : European Commission NEUROPAIN Grant

ID : 602891

Informations de copyright

Références

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