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Investigating the g...
Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study
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- Guerreiro, R. (author)
- University of Aveiro,University College London
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- Ross, O. A. (author)
- Mayo Clinic Florida,University of Oxford
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- Kun-Rodrigues, C. (author)
- University College London
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- Hernandez, D. G. (author)
- German Center for Neurodegenerative Diseases (DZNE), Bonn,National Institutes of Health, United States,University of California, San Diego,Veterans Health Administration
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- Orme, T. (author)
- University College London
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- Eicher, J. D. (author)
- Merck Sharp And Dohme Corp., US
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- Shepherd, C. E. (author)
- University of New South Wales
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- Parkkinen, L. (author)
- University of Oxford
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- Darwent, L. (author)
- University College London
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- Heckman, M. G. (author)
- Mayo Clinic Florida
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- Scholz, S. W. (author)
- National Institutes of Health, United States
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- Troncoso, J. C. (author)
- Johns Hopkins University School of Medicine,CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona
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- Pletnikova, O. (author)
- Johns Hopkins University School of Medicine
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Ansorge, O. (author)
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- Clarimon, J. (author)
- Washington University in St. Louis
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- Lleo, A. (author)
- Autonomous University of Barcelona,CIBER Enfermedades Neurodegenerativas (CIBERNED)
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- Morenas-Rodriguez, E. (author)
- Autonomous University of Barcelona,CIBER Enfermedades Neurodegenerativas (CIBERNED)
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- Clark, L. (author)
- Columbia University
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- Honig, L. S. (author)
- Columbia University,Pitié-Salpêtrière University Hospital
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- Marder, K. (author)
- Columbia University
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- Lemstra, A. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Rogaeva, E. (author)
- University of Toronto
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- St George-Hyslop, P. (author)
- University of Cambridge,University of Toronto,Mutua De Terrassa Hospital,Autonomous University of Barcelona
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- Londos, Elisabet (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University College London,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Barber, I. (author)
- University of Nottingham
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- Braae, A. (author)
- University of Nottingham
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- Brown, K. (author)
- University of Nottingham
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- Morgan, K. (author)
- University of Nottingham
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- Troakes, C. (author)
- King's College London
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- Al-Sarraj, S. (author)
- King's College London
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- Lashley, T. (author)
- University College London
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- Holton, J. (author)
- University College London
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- Compta, Y. (author)
- University College London,University of Barcelona
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- Van Deerlin, V. (author)
- University of Pennsylvania
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- Serrano, G. E. (author)
- Banner Sun Health Research Institute
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- Beach, T. G. (author)
- Banner Sun Health Research Institute
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Lesage, S. (author)
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Galasko, D. (author)
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- Masliah, E. (author)
- National Institutes of Health, United States
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- Santana, I. (author)
- University of Coimbra
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Pastor, P. (author)
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- Diez-Fairen, M. (author)
- Autonomous University of Barcelona,Mutua De Terrassa Hospital
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- Aguilar, M. (author)
- Mutua De Terrassa Hospital,Autonomous University of Barcelona
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- Tienari, P. J. (author)
- Helsinki University Central Hospital,University of Helsinki
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- Myllykangas, L. (author)
- University of Helsinki Haartman Institute,Helsinki University Central Hospital
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- Oinas, M. (author)
- University of Helsinki,Helsinki University Central Hospital
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- Revesz, T. (author)
- University College London
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- Lees, A. (author)
- University College London
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- Boeve, B. F. (author)
- Mayo Clinic Minnesota
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- Petersen, R. C. (author)
- Mayo Clinic Minnesota
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- Ferman, T. J. (author)
- Mayo Clinic Florida
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- Escott-Price, V. (author)
- Cardiff University
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- Graff-Radford, N. (author)
- Mayo Clinic Florida
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- Cairns, N. J. (author)
- Washington University in St. Louis
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Morris, J. C. (author)
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- Pickering-Brown, S. (author)
- University of Manchester
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- Mann, D. (author)
- University of Manchester
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- Halliday, G. M. (author)
- University of Sydney,University of New South Wales
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- Hardy, J. (author)
- University College London
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- Trojanowski, J. Q. (author)
- University of Pennsylvania
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- Dickson, D. W. (author)
- Mayo Clinic Florida
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- Singleton, A. (author)
- National Institutes of Health, United States
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- Stone, D. J. (author)
- Merck Sharp And Dohme Corp., US
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- Bras, J. (author)
- University of Aveiro,University College London
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(creator_code:org_t)
- 2018
- 2018
- English.
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In: Lancet Neurology. - 1474-4422. ; 17:1, s. 64-74
- Related links:
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http://dx.doi.org/10...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI 2.14-2.70; p=1.05 x 10-48), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x 10(-10)), and GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- genotype imputation
- parkinsons-disease
- alzheimers-disease
- risk
- mutations
- protein
- heritability
- consortium
- haplotypes
- pathology
- Neurosciences & Neurology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Guerreiro, R.
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Ross, O. A.
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Kun-Rodrigues, C ...
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Hernandez, D. G.
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Orme, T.
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Eicher, J. D.
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show more...
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Shepherd, C. E.
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Parkkinen, L.
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Darwent, L.
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Heckman, M. G.
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Scholz, S. W.
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Troncoso, J. C.
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Pletnikova, O.
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Ansorge, O.
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Clarimon, J.
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Lleo, A.
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Morenas-Rodrigue ...
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Clark, L.
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Honig, L. S.
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Marder, K.
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Lemstra, A.
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Rogaeva, E.
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St George-Hyslop ...
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Londos, Elisabet
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Zetterberg, Henr ...
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Barber, I.
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Braae, A.
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Brown, K.
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Morgan, K.
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Troakes, C.
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Al-Sarraj, S.
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Lashley, T.
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Holton, J.
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Compta, Y.
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Van Deerlin, V.
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Serrano, G. E.
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Beach, T. G.
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Lesage, S.
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Galasko, D.
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Masliah, E.
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Santana, I.
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Pastor, P.
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Diez-Fairen, M.
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Aguilar, M.
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Tienari, P. J.
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Myllykangas, L.
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Oinas, M.
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Revesz, T.
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Lees, A.
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Boeve, B. F.
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Petersen, R. C.
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Ferman, T. J.
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Escott-Price, V.
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Graff-Radford, N ...
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Cairns, N. J.
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Morris, J. C.
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Pickering-Brown, ...
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Mann, D.
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Halliday, G. M.
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Hardy, J.
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Trojanowski, J. ...
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Dickson, D. W.
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Singleton, A.
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Stone, D. J.
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Bras, J.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Lancet Neurology
- By the university
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University of Gothenburg
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Lund University