Association of Essential Tremor With Novel Risk Loci: A Genome-Wide Association Study and Meta-analysis.

Autor:	Liao C; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Castonguay CE; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada., Heilbron K; 23andMe, Inc, Sunnyvale, California., Vuokila V; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Medeiros M; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Houle G; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Akçimen F; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Ross JP; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Catoire H; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Diez-Fairen M; Fundació Docència i Recerca Mútua Terrassa, University Hospital Mútua de Terrassa, Terrassa, Barcelona, Spain.; Movement Disorders Unit, Department of Neurology, University Hospital Mútua de Terrassa, Terrassa, Barcelona, Spain., Kang J; Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee., Mueller SH; Institute of Health Informatics, University College London, London, United Kingdom., Girard SL; Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada., Hopfner F; Department of Neurology, Hannover Medical School, Hannover, Germany., Lorenz D; University Children's Hospital, University of Würzburg, Wurzburg, Germany., Clark LN; Department of Pathology and Cell Biology, Taub Institute, Columbia University, New York, New York., Soto-Beasley AI; Department of Neurology, Mayo Clinic Florida, Jacksonville., Klebe S; Department of Neurology, University Hospital Würzburg, Wurzburg, Germany.; Department of Neurology, University Hospital Essen, Essen, Germany., Hallett M; National Institute of Neurological Disorders and Stroke Intramural Research Program, National Institutes of Health, Bethesda, Maryland., Wszolek ZK; Department of Neurology, Mayo Clinic Florida, Jacksonville., Pendziwiat M; Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany.; Department of Neuropediatrics, University Medical Center Schleswig-Holstein, University of Kiel, Kiel, Germany., Lorenzo-Betancor O; Veterans Affairs Puget Sound Health Care System, Seattle, Washington.; Department of Neurology, University of Washington School of Medicine, Seattle., Seppi K; Department of Neurology, Innsbruck Medical University, Innsbruck, Austria., Berg D; Department of Neurology, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany., Vilariño-Güell C; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada., Postuma RB; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada., Bernard G; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.; Division of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurosurgery, Montreal Children's Hospital, Montreal, Quebec, Canada.; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.; Division of Medical Genetics, Department of Specialized Medicine, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada., Dupré N; Faculté de Médecine, Université Laval, Centre Hospitalier Universitaire de Québec (l'Enfant-Jésus), Quebec, Canada., Jankovic J; Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas., Testa CM; Parkinson's and Movement Disorders Center, Department of Neurology, Virginia Commonwealth University, Richmond., Ross OA; Departments of Neuroscience and Clinical Genomics, Mayo Clinic Florida, Jacksonville., Arzberger T; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.; Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich, Germany., Chouinard S; Unité des troubles du mouvement André Barbeau, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada., Louis ED; Department of Neurology, The University of Texas Southwestern Medical Center, Dallas., Mandich P; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health (DINOGMI), University of Genoa, Genova, Italy.; Istituto di Ricovero e Cura a Carattere Scientifico Policlinico, San Martino, Genova, Italy., Vitale C; Department of Motor Sciences and Wellness, University Parthenope, Naples, Italy., Barone P; Center for Neurodegenerative Disease (CEMAND), Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Salerno, Italy., García-Martín E; University Institute of Molecular Pathology Biomarkers, UNEx, ARADyAL Instituto de Salud Carlos III, Caceres, Spain., Alonso-Navarro H; Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain., Agúndez JAG; University Institute of Molecular Pathology Biomarkers, UNEx, ARADyAL Instituto de Salud Carlos III, Caceres, Spain., Jiménez-Jiménez FJ; Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain., Pastor P; Fundació Docència i Recerca Mútua Terrassa, University Hospital Mútua de Terrassa, Terrassa, Barcelona, Spain., Rajput A; University of Saskatchewan, Saskatoon Health Authority, Saskatoon, Saskatchewan, Canada., Deuschl G; Department of Neurology, University Medical Center Schleswig Holstein, University of Kiel, Kiel, Germany., Kuhlenbaümer G; Department of Neurology, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany., Meijer IA; Department of Neuroscience and Pediatrics, Université de Montréal, Montreal, Quebec, Canada., Dion PA; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada., Rouleau GA; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Jazyk:	angličtina
Zdroj:	JAMA neurology [JAMA Neurol] 2022 Feb 01; Vol. 79 (2), pp. 185-193.
DOI:	10.1001/jamaneurol.2021.4781
Abstrakt:	Importance: Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified. Objective: To identify common genetic factors associated with risk of ET. Design, Setting, and Participants: Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicenter samples collected from European populations were collected from January 2010 to September 2019 as part of an ongoing study. Included patients were clinically diagnosed with or reported having ET. Control individuals were not diagnosed with or reported to have ET. Of 485 250 individuals, data for 483 054 passed data quality control and were used. Main Outcomes and Measures: Genotypes of common variants associated with risk of ET. Results: Of the 483 054 individuals included, there were 7177 with ET (3693 [51.46%] female; mean [SD] age, 62.66 [15.12] years), and 475 877 control individuals (253 785 [53.33%] female; mean [SD] age, 56.40 [17.6] years). Five independent genome-wide significant loci and were identified and were associated with approximately 18% of ET heritability. Functional analyses found significant enrichment in the cerebellar hemisphere, cerebellum, and axonogenesis pathways. Genetic correlation (r), which measures the degree of genetic overlap, revealed significant common variant overlap with Parkinson disease (r, 0.28; P = 2.38 × 10-8) and depression (r, 0.12; P = 9.78 × 10-4). A separate fine-mapping of transcriptome-wide association hits identified genes such as BACE2, LRRN2, DHRS13, and LINC00323 in disease-relevant brain regions, such as the cerebellum. Conclusions and Relevance: The results of this genome-wide association study suggest that a portion of ET heritability can be explained by common genetic variation and can help identify new common genetic risk factors for ET.
Databáze:	MEDLINE
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