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

Autor:	Åkerlund M; Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Lund, Sweden., Baskozos G; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Li W; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Themistocleous AC; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Pascal MMV; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Rayner NW; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, United Kingdom.; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.; Department of Human Genetics, Wellcome Sanger Institute, Hinxton, United Kingdom.; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Attal N; INSERM U987, APHP and UVSQ Paris Saclay University, CHU Ambroise Paré, Boulogne Billancourt, France., Baron R; Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany., Baudic S; INSERM U987, APHP and UVSQ Paris Saclay University, CHU Ambroise Paré, Boulogne Billancourt, France., Bennedsgaard K; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark., Bouhassira D; INSERM U987, APHP and UVSQ Paris Saclay University, CHU Ambroise Paré, Boulogne Billancourt, France., Comini M; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Crombez G; Department of Experimental-Clinical and Health Psychology, Ghent University, Ghent, Belgium., Faber CG; Department of Neurology, Maastricht University Medical Center, Mental Health and Neuroscience Reseach Institute, Maastricht, the Netherlands., Finnerup NB; Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark.; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark., Gierthmühlen J; Department for Anesthesiology and Surgical Intensive Care Medicine, Pain Therapy, University Hospital of Kiel, Kiel, Germany., Granovsky Y; Department of Neurology, Rambam Health Care Campus, Technion-Israel Institute of Technology, Haifa, Israel., Gylfadottir SS; Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark.; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark., Hébert HL; Chronic Pain Research Group, Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom., Jensen TS; Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark.; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark., John J; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom., Kemp HI; Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom., Lauria G; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.; Department of Clinical Neurosciences, IRCCS Fondazione Istituto Neurologico 'Carlo Besta,' Milan, Italy., Laycock H; Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom., Meng W; Chronic Pain Research Group, Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.; Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, China., Nilsen KB; Section for Clinical Neurophysiology, Department of Neurology, Oslo University Hospital, Oslo, Norway., Palmer C; Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom., Rice ASC; Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom., Serra J; Department of Clinical Neurophysiology, King's College Hospital, London, United Kingdom., Smith BH; Chronic Pain Research Group, Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom., Tesfaye S; Diabetes Research Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Topaz LS; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel., Veluchamy A; Chronic Pain Research Group, Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom., Vollert J; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom., Yarnitsky D; Department of Neurology, Rambam Health Care Campus, Technion-Israel Institute of Technology, Haifa, Israel., van Zuydam N; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Zwart JA; Department of Research and Innovation, Oslo University Hospital and University of Oslo, Oslo, Norway., McCarthy MI; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, United Kingdom.; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Lyssenko V; Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Lund, Sweden.; Department of Clinical Science, University of Bergen, Bergen, Norway., Bennett DL; Nuffield Department of Clinical Neuroscience, The University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI:	10.1097/j.pain.0000000000003463
Abstrakt:	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 = 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. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)
Databáze:	MEDLINE
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