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Nat Genet. 2016 Oct;48(10):1279-83. doi: 10.1038/ng.3643. Epub 2016 Aug 22.

A reference panel of 64,976 haplotypes for genotype imputation.

McCarthy S1, Das S2,3, Kretzschmar W4, Delaneau O5, Wood AR6, Teumer A7,8, Kang HM2,3, Fuchsberger C2,3, Danecek P9, Sharp K10, Luo Y1, Sidore C11, Kwong A2,3, Timpson N12, Koskinen S13, Vrieze S14,15, Scott LJ2,3, Zhang H16, Mahajan A4, Veldink J17, Peters U18,19, Pato C20, van Duijn CM21, Gillies CE22, Gandin I23, Mezzavilla M24,25, Gilly A1, Cocca M23, Traglia M26, Angius A11, Barrett JC1, Boomsma D27, Branham K28, Breen G29,30, Brummett CM31, Busonero F11, Campbell H32, Chan A32,33, Chen S2,3,34,35, Chew E36, Collins FS37, Corbin LJ12, Smith GD12, Dedoussis G38, Dorr M39,40, Farmaki AE38, Ferrucci L41, Forer L42, Fraser RM31, Gabriel S43, Levy S44, Groop L45,46,47, Harrison T18, Hattersley A48, Holmen OL49, Hveem K49, Kretzler M34,35,50, Lee JC51,52, McGue M53, Meitinger T54,55,56, Melzer D57, Min JL12, Mohlke KL58, Vincent JB59,60,61, Nauck M8,40, Nickerson D62, Palotie A43,63,64,65,66,67, Pato M20, Pirastu N23, McInnis M68, Richards JB69,70,71, Sala C26, Salomaa V13, Schlessinger D72, Schoenherr S42, Slagboom PE73, Small K71, Spector T71, Stambolian D74, Tuke M6, Tuomilehto J75,76,77,78, Van den Berg LH17, Van Rheenen W17, Volker U40,79, Wijmenga C80, Toniolo D26, Zeggini E1, Gasparini P23,25, Sampson MG22, Wilson JF32,81, Frayling T6, de Bakker PI82,83, Swertz MA80,84, McCarroll S85,86, Kooperberg C18, Dekker A17, Altshuler D43,65,87,88,89,90, Willer C16,34,35, Iacono W53, Ripatti S91, Soranzo N1,92,93, Walter K1, Swaroop A94, Cucca F11, Anderson CA1, Myers RM44, Boehnke M2,3, McCarthy MI4,95,96, Durbin R1; Haplotype Reference Consortium.

Author information

1
Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
2
Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
3
Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
4
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
5
Genetics and Development, University of Geneva, Geneva, Switzerland.
6
Genetics of Complex Traits, Institute of Biomedical Science, University of Exeter Medical School, Exeter, UK.
7
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
8
DZHK (German Centre for Cardiovascular Research), Greifswald, Germany.
9
Vertebrate Resequencing Informatics, Wellcome Trust Sanger Institute, Hinxton, UK.
10
Department of Statistics, University of Oxford, Oxford, UK.
11
IRGB, CNR, Sardinia, Italy.
12
MRC Integrative Epidemiology Unit, University of Bristol, Oakfield Grove, UK.
13
THL, Helsinki, Finland.
14
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA.
15
Department of Psychology and Neurosurgery, University of Colorado, Boulder, Colorado, USA.
16
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
17
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht, the Netherlands.
18
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
19
Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA.
20
Department of Psychiatry, SUNY Downstate, Brooklyn, New York, USA.
21
Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
22
Department of Pediatrics-Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
23
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
24
Genetica Medica, IRCCS Burlo Garofolo, Trieste, Italy.
25
Department of Experimental Genetics, Sidra, Doha, Qatar.
26
Genetics and Cell Biology, San Raffaele Research Institute, Milan, Italy.
27
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
28
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
29
MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
30
NIHR Biomedical Research Centre for Mental Health, Institute of Psychiatry, Psychology and Neuroscience, King's College London and the South London Maudsley Hospital, London, UK.
31
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA.
32
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
33
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
34
Department of Computational Medicine, University of Michigan, Ann Arbor, Michigan, USA.
35
Department of Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
36
Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, USA.
37
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.
38
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
39
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
40
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
41
Longitudinal Studies Section, Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA.
42
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
43
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
44
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
45
Department of Clinical Sciences, Diabetes and Endocrinology, University of Lund, Malmö, Sweden.
46
Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
47
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
48
Institute of Biomedical and Clinical Research, University of Exeter Medical School, Exeter, UK.
49
Hunt Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
50
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
51
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
52
Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
53
Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
54
Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
55
Institute of Human Genetics, Technische Universität München, Munich, Germany.
56
DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
57
Epidemiology and Public Health, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
58
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
59
Molecular Neuropsychiatry and Development Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
60
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
61
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
62
Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
63
Institute for Molecular Medicine, FIMM, Helsinki, Finland.
64
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
65
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
66
Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
67
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
68
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA.
69
Department of Medicine, McGill University, Montreal, Quebec, Canada.
70
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
71
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
72
National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.
73
Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
74
Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
75
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
76
Dasman Diabetes Institute, Dasman, Kuwait.
77
Center for Vascular Prevention, Danube University Krems, Krems, Austria.
78
Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
79
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
80
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
81
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
82
Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
83
Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
84
University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
85
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
86
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
87
Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
88
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
89
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
90
Vertex Pharmaceuticals, Boston, Massachusetts, USA.
91
Department of Public Health, University of Helsinki, Helsinki, Finland.
92
Department of Haematology, University of Cambridge, Cambridge, UK.
93
NIHR Blood and Transplant Unit (BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
94
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, US National Institutes of Health, Bethesda, Maryland, USA.
95
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
96
Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, UK.

Abstract

We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.

PMID:
27548312
PMCID:
PMC5388176
DOI:
10.1038/ng.3643
[Indexed for MEDLINE]
Free PMC Article

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