MARC

LEADER 00000nab a2200000uu 4500
001 2104154166
003 UK-CbPIL
022 |a 1018-4813 
022 |a 1476-5438 
024 7 |a 10.1038/s41431-018-0177-4  |2 doi 
035 |a 2104154166 
045 2 |b d20181001  |b d20181031 
084 |a 68901  |2 nlm 
100 1 |a Wouter Van Rheenen  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
245 1 |a Project MinE: study design and pilot analyses of a large-scale whole-genome sequencing study in amyotrophic lateral sclerosis 
260 |b Nature Publishing Group  |c Oct 2018 
513 |a Journal Article 
520 3 |a The most recent genome-wide association study in amyotrophic lateral sclerosis (ALS) demonstrates a disproportionate contribution from low-frequency variants to genetic susceptibility to disease. We have therefore begun Project MinE, an international collaboration that seeks to analyze whole-genome sequence data of at least 15 000 ALS patients and 7500 controls. Here, we report on the design of Project MinE and pilot analyses of successfully sequenced 1169 ALS patients and 608 controls drawn from the Netherlands. As has become characteristic of sequencing studies, we find an abundance of rare genetic variation (minor allele frequency < 0.1%), the vast majority of which is absent in public datasets. Principal component analysis reveals local geographical clustering of these variants within The Netherlands. We use the whole-genome sequence data to explore the implications of poor geographical matching of cases and controls in a sequence-based disease study and to investigate how ancestry-matched, externally sequenced controls can induce false positive associations. Also, we have publicly released genome-wide minor allele counts in cases and controls, as well as results from genic burden tests. 
651 4 |a Netherlands 
653 |a Data processing 
653 |a Amyotrophic lateral sclerosis 
653 |a Genomes 
653 |a Nucleotide sequence 
653 |a Gene frequency 
653 |a Genetic diversity 
653 |a Alleles 
653 |a Genome-wide association studies 
700 1 |a Pulit, Sara L  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Dekker, Annelot M  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Ahmad Al Khleifat  |u Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK 
700 1 |a Brands, William J  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Iacoangeli, Alfredo  |u Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK 
700 1 |a Kenna, Kevin P  |u Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA 
700 1 |a Kavak, Ersen  |u Genomize Inc. Bogazici University, Technology Transfer Region, ETAB, Istanbul, Turkey 
700 1 |a Kooyman, Maarten  |u SURFsara, Amsterdam, The Netherlands 
700 1 |a McLaughlin, Russell L  |u Population Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland 
700 1 |a Middelkoop, Bas  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Moisse, Matthieu  |u Department of Neurosciences, KU Leuven - University of Leuven, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium 
700 1 |a Schellevis, Raymond D  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Shatunov, Aleksey  |u Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK 
700 1 |a Sproviero, William  |u Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK 
700 1 |a Tazelaar, Gijs H P  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Rick A A Van der Spek  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Perry T C Van Doormaal  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Van Eijk, Kristel R  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Joke Van Vugt  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Basak, A Nazli  |u Neurodegeneration Research Laboratory, Bogazici University, Istanbul, Turkey 
700 1 |a Blair, Ian P  |u Centre for Motor Neuron Disease Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia 
700 1 |a Glass, Jonathan D  |u Department Neurology, Emory University School of Medicine, Atlanta, GA, USA; Emory ALS Center, Emory University School of Medicine, Atlanta, GA, USA 
700 1 |a Hardiman, Orla  |u Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland; Department of Neurology, Beaumont Hospital, Dublin, Ireland 
700 1 |a Hide, Winston  |u Biostatistics Department, Harvard School of Public Health, Boston, MA, USA; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK 
700 1 |a Landers, John E  |u Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA 
700 1 |a Mora, Jesus S  |u Department of Neurology, Hospital San Rafael, Madrid, Spain 
700 1 |a Morrison, Karen E  |u Faculty of Medicine, University of Southampton, Southampton, UK 
700 1 |a Newhouse, Stephen  |u Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, UK 
700 1 |a Robberecht, Wim  |u VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven - University of Leuven, Leuven, Belgium 
700 1 |a Shaw, Christopher E  |u Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK 
700 1 |a Shaw, Pamela J  |u Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK 
700 1 |a Philip Van Damme  |u VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven, Belgium; Department of Neurology, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven - University of Leuven, Leuven, Belgium 
700 1 |a Van Es, Michael A  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Wray, Naomi R  |u Queensland Brain Institute, The University of Queensland, Brisbane, Qld, Australia 
700 1 |a Al-Chalabi, Ammar  |u Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, UK 
700 1 |a Leonard H Van den Berg  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
700 1 |a Veldink, Jan H  |u Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands 
773 0 |t European Journal of Human Genetics : EJHG  |g vol. 26, no. 10 (Oct 2018), p. 1537 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/2104154166/abstract/embedded/75I98GEZK8WCJMPQ?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/2104154166/fulltextPDF/embedded/75I98GEZK8WCJMPQ?source=fedsrch