In EDS ansehen

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

Gespeichert in:
Bibliographische Detailangaben
Titel: Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort
Autoren: Akerlund, Mikael, Baskozos, Georgios, Li, Wenqianglong, Themistocleous, Andreas C., Pascal, Mathilde M.V., Rayner, N. William, Attal, Nadine, Baron, Ralf, Baudic, Sophie, Bennedsgaard, Kristine, Bouhassira, Didier, Comini, Maddalena, Crombez, Geert, Faber, Catharina G., Finnerup, Nanna B., Gierthmühlen, Janne, Granovsky, Yelena, Gylfadottir, Sandra Sif, Hébert, Harry L., Jensen, Troels S., John, Jishi, Kemp, Harriet I., Lauria, Giuseppe, Laycock, Helen, Meng, Weihua, Nilsen, Kristian Bernhard, Palmer, Colin, Rice, Andrew S.C., Serra, Jordi, Smith, Blair H., Tesfaye, Solomon, Topaz, Leah Shafran, Veluchamy, Abirami, Vollert, Jan, Yarnitsky, David, van Zuydam, Natalie, Zwart, John Anker, McCarthy, Mark I., Lyssenko, Valeriya, Bennett, David L.
Weitere Verfasser: Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Translational Diabetes Research, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Translationell diabetesforskning, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EXODIAB: Excellence of Diabetes Research in Sweden, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EXODIAB: Excellence of Diabetes Research in Sweden, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Malmö, Translational Muscle Research, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Malmö, Translationell muskelforskning, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator
Quelle: Pain. 166(6):1354-1368
Schlagwörter: Medical and Health Sciences, Basic Medicine, Medical Genetics and Genomics (including Gene Therapy), Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik och genomik (Här ingår: Genterapi)
Beschreibung: 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 5 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P 5 3.55 3 1028). 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 5 4.39 3 1028) 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.
Zugangs-URL: https://doi.org/10.1097/j.pain.0000000000003463
Datenbank: SwePub
Beschreibung
Abstract: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 5 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P 5 3.55 3 1028). 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 5 4.39 3 1028) 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.
ISSN:03043959
18726623
DOI:10.1097/j.pain.0000000000003463