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Åkerlund, M.* ; Baskozos, G.* ; Li, W.* ; Themistocleous, A.C.* ; Pascal, M.M.V.* ; Rayner, N.W. ; Attal, N.* ; Baron, R.* ; Baudic, S.* ; Bennedsgaard, K.* ; Bouhassira, D.* ; Comini, M.* ; Crombez, G.* ; Faber, C.G.* ; Finnerup, N.B.* ; Gierthmühlen, J.* ; Granovsky, Y.* ; Gylfadottir, S.S.* ; Hébert, H.L.* ; Jensen, T.S.* ; John, J.* ; Kemp, H.I.* ; Lauria, G.* ; Laycock, H.* ; Meng, W.* ; Nilsen, K.B.* ; Palmer, C.* ; Rice, A.S.C.* ; Serra, J.* ; Smith, B.H.* ; Tesfaye, S.* ; Topaz, L.S.* ; Veluchamy, A.* ; Vollert, J.* ; Yarnitsky, D.* ; van Zuydam, N.* ; Zwart, J.A.* ; McCarthy, M.I.* ; Lyssenko, V.* ; Bennett, D.L.*

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

Pain 166, 1354-1368 (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Diabetes Mellitus ; Gwas ; Neuropathic Pain ; Neuropathy ; Scn9a ; Sensory Profile; Genome-wide Association; Opioid Receptor; Sodium-channels; Scn9a Variants; Mutation; Protein; Symptoms; Tcf7l2
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 0304-3959
e-ISSN 1872-6623
Zeitschrift Pain
Quellenangaben Band: 166, Heft: 6, Seiten: 1354-1368 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506700-001
Förderungen Wellcome Trust
DOI 10.1097/j.pain.0000000000003463
WOS ID 001486839400006
Scopus ID 85208221634
PubMed ID 39471050
Erfassungsdatum 2024-10-30
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