Abstract

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

The association between blood pressure (BP) and migraine is poorly understood. Here, the authors explore this relationship using summary-level GWAS data for BP and migraine. Cross-trait meta-analysis reveals shared loci between BP and migraine, while Mendelian randomization suggests that diastolic BP specifically plays a key role in migraine susceptibility.

Details

Title
A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine
Author
Guo Yanjun 1   VIAFID ORCID Logo  ; Rist, Pamela M 1 ; Iyas, Daghlas 2 ; Giulianini Franco 3 ; Gormley Padhraig 4 ; Anttila Verneri 5 ; Winsvold Bendik S 6 ; Palta Priit 7 ; Tonu, Esko 8 ; Pers Tune H 9 ; Kai-How, Farh 10 ; Cuenca-Leon, Ester 11 ; Muona Mikko 12 ; Furlotte, Nicholas A 13 ; Kurth, Tobias 14 ; Ingason Andres 15 ; McMahon, George 16 ; Ligthart Lannie 17 ; Terwindt, Gisela M 18 ; Kallela Mikko 19 ; Freilinger, Tobias M 20 ; Ran, Caroline 21 ; Gordon, Scott G 22 ; Stam, Anine H 18 ; Steinberg, Stacy 15 ; Borck Guntram 23 ; Koiranen Markku 24 ; Quaye Lydia 25 ; Adams Hieab H H 26 ; Lehtimäki Terho 27 ; Sarin Antti-Pekka 7 ; Wedenoja Juho 28 ; Hinds, David A 13 ; Buring, Julie E 2 ; Schürks Markus 29 ; Ridker Paul M 2 ; Hrafnsdottir Maria Gudlaug 30 ; Stefansson Hreinn 15 ; Ring, Susan M 16 ; Jouke-Jan, Hottenga 17 ; Penninx Brenda W J H 31 ; Färkkilä Markus 19 ; Artto Ville 19 ; Kaunisto Mari 7 ; Vepsäläinen Salli 19 ; Malik, Rainer 32 ; Heath, Andrew C 33 ; Madden Pamela A F 33 ; Martin, Nicholas G 22 ; Montgomery, Grant W 22 ; Kurki Mitja 34 ; Kals Mart 35 ; Reedik, Mägi 35 ; Pärn Kalle 35 ; Hämäläinen Eija 7 ; Huang, Hailiang 5 ; Byrnes, Andrea E 5 ; Franke Lude 36 ; Huang, Jie 37 ; Stergiakouli Evie 16 ; Lee, Phil H 34 ; Sandor, Cynthia 38 ; Webber, Caleb 38 ; Cader Zameel 39 ; Muller-Myhsok Bertram 40 ; Schreiber, Stefan 41 ; Meitinger, Thomas 42 ; Eriksson, Johan G 43 ; Salomaa Veikko 44 ; Heikkilä Kauko 45 ; Loehrer, Elizabeth 46 ; Uitterlinden, Andre G 47 ; Hofman, Albert 48 ; Duijn Cornelia M van 48 ; Cherkas, Lynn 25 ; Pedersen, Linda M 49 ; Stubhaug Audun 50 ; Nielsen, Christopher S 51 ; Männikkö Minna 24 ; Mihailov Evelin 35 ; Milani Lili 35 ; Göbel Hartmut 52 ; Ann-Louise, Esserlind 53 ; Christensen Anne Francke 53 ; Hansen, Thomas Folkmann 54 ; Werge, Thomas 55 ; Kaprio Jaakko 56 ; Aromaa Arpo J 44 ; Raitakari Olli 57 ; Arfan, Ikram M 58 ; Spector, Tim 25 ; Järvelin Marjo-Riitta 59 ; Metspalu Andres 35 ; Kubisch, Christian 60 ; Strachan, David P 61 ; Ferrari, Michel D 18 ; Belin, Andrea C 21 ; Dichgans Martin 62 ; Wessman Maija 63 ; Maagdenberg Arn M J M van den 64 ; John-Anker, Zwart 6 ; Boomsma Dorret I 17 ; Smith, George Davey 16 ; Stefansson Kari 65 ; Eriksson, Nicholas 13 ; Daly, Mark J 5 ; Neale, Benjamin M 5 ; Olesen Jes 66 ; Chasman, Daniel I 2 ; Nyholt Dale R 67 ; Palotie Aarno 68 ; Agee, Michelle 13 ; Auton, Adam 13 ; Bell, Robert K 13 ; Bryc Katarzyna 13 ; Elson, Sarah L 13 ; Fontanillas Pierre 13 ; Huber, Karen E 13 ; Kleinman, Aaron 13 ; Litterman, Nadia K 13 ; McCreight, Jennifer C 13 ; McIntyre, Matthew H 13 ; Mountain, Joanna L 13 ; Noblin, Elizabeth S 13 ; Northover Carrie A M 13 ; Pitts, Steven J 13 ; Fah, Sathirapongsasuti J 13 ; Sazonova, Olga V 13 ; Shelton, Janie F 13 ; Shringarpure Suyash 13 ; Tian, Chao 13 ; Tung, Joyce Y 13 ; Vacic Vladimir 13 

1  Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
2  Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
3  Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
4  Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382) 
5  Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
6  FORMI, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Department of Neurology, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Institute of Clinical Medicine, University of Oslo, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
7  Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
8  Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Estonian Genome Center, University of Tartu, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661); Division of Endocrinology, Boston Children’s Hospital, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438) 
9  Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Division of Endocrinology, Boston Children’s Hospital, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (GRID:grid.6203.7) (ISNI:0000 0004 0417 4147); Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
10  Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Illumina, San Diego, USA (GRID:grid.185669.5) (ISNI:0000 0004 0507 3954) 
11  Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Vall d’Hebron Research Institute, Pediatric Neurology, Barcelona, Spain (GRID:grid.430994.3) (ISNI:0000 0004 1763 0287) 
12  Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Folkhälsan Institute of Genetics, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Neuroscience Center, University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
13  23andMe, Inc., Sunnyvale, USA (GRID:grid.420283.f) (ISNI:0000 0004 0626 0858) 
14  Inserm Research Center for Epidemiology and Biostatistics (U897), University of Bordeaux, Bordeaux, France (GRID:grid.412041.2) (ISNI:0000 0001 2106 639X); Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
15  deCODE Genetics, Reykjavik, Iceland (GRID:grid.421812.c) (ISNI:0000 0004 0618 6889) 
16  Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
17  Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227) 
18  Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
19  Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland (GRID:grid.15485.3d) (ISNI:0000 0000 9950 5666) 
20  Institute for Stroke and Dementia Research, Klinikum der Universtität München, Ludwig-Maximilians-Universität München, Munich, Germany (GRID:grid.15485.3d); Department of Neurology and Epileptology, Hertie Institute for Clincal Brain Research, University of Tuebingen, Tuebingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447) 
21  Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
22  Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
23  Institute of Human Genetics, Ulm University, Ulm, Germany (GRID:grid.6582.9) (ISNI:0000 0004 1936 9748) 
24  Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873) 
25  Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
26  Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
27  Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254) 
28  Department of Public Health, University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
29  University Duisburg Essen, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445) 
30  Landspitali University Hospital, Reykjavik, Iceland (GRID:grid.410540.4) (ISNI:0000 0000 9894 0842) 
31  Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands (GRID:grid.16872.3a) (ISNI:0000 0004 0435 165X) 
32  Institute for Stroke and Dementia Research, Klinikum der Universtität München, Ludwig-Maximilians-Universität München, Munich, Germany (GRID:grid.15485.3d) 
33  Department of Psychiatry, Washington University School of Medicine, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
34  Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) 
35  Estonian Genome Center, University of Tartu, Tartu, Estonia (GRID:grid.10939.32) (ISNI:0000 0001 0943 7661) 
36  University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (GRID:grid.32224.35) 
37  Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382) 
38  MRC Functional Genomics Unit, Department of Physiology, Anatomy & Genetics, Oxford University, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
39  Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); Oxford Headache Centre, John Radcliffe Hospital, Oxford, UK (GRID:grid.8348.7) (ISNI:0000 0001 2306 7492) 
40  Max-Planck-Institute of Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095) 
41  Christian Albrechts University, Kiel, Germany (GRID:grid.9764.c) (ISNI:0000 0001 2153 9986) 
42  Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
43  Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (GRID:grid.15485.3d) (ISNI:0000 0000 9950 5666); National Institute for Health and Welfare, Helsinki, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499) 
44  National Institute for Health and Welfare, Helsinki, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499) 
45  Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
46  Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
47  Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
48  Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
49  FORMI, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
50  Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Medical Faculty, University of Oslo, Oslo, Norway (GRID:grid.55325.34) 
51  Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway (GRID:grid.418193.6) (ISNI:0000 0001 1541 4204) 
52  Kiel Pain and Headache Center, Kiel, Germany (GRID:grid.10939.32) 
53  Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (GRID:grid.10939.32) 
54  Institute of Biological Psychiatry, Mental Health Center Sct. Hans, University of Copenhagen, Roskilde, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
55  Institute Of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Copenhagen, Denmark (GRID:grid.5254.6); Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); iPSYCH - The Lundbeck Foundation’s Initiative for Integrative Psychiatric Research, Copenhagen, Denmark (GRID:grid.5254.6) 
56  Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Department of Public Health, University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Department of Health, National Institute for Health and Welfare, Helsinki, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499) 
57  Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland (GRID:grid.410552.7) (ISNI:0000 0004 0628 215X) 
58  Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland (GRID:grid.410552.7) (ISNI:0000 0004 0628 215X); Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
59  Center for Life Course Epidemiology and Systems Medicine, University of Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Biocenter Oulu, University of Oulu, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); Unit of Primary Care, Oulu University Hospital, Oulu, Finland (GRID:grid.412326.0) (ISNI:0000 0004 4685 4917) 
60  University Medical Center Hamburg Eppendorf, Institute of Human Genetics, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484) 
61  Population Health Research Institute, St George’s, University of London, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201) 
62  Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (GRID:grid.452617.3) 
63  Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Folkhälsan Institute of Genetics, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
64  Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978); Leiden University Medical Centre, Department of Human Genetics, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
65  deCODE Genetics, Reykjavik, Iceland (GRID:grid.421812.c) (ISNI:0000 0004 0618 6889); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (GRID:grid.14013.37) (ISNI:0000 0004 0640 0021) 
66  Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (GRID:grid.32224.35) 
67  Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
68  Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK (GRID:grid.10306.34) (ISNI:0000 0004 0606 5382); Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603); Department of Neurology, Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-17002-0
ProQuest document ID
2420335240
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.