Capítulo IV: Resultados
5.2. Recomendaciones
as the dotted red line. Variants with association P < 5 × 10-7 are coloured red. P values are from a Score test and have genomic control applied unless minor allele count (MAC) < 400 and Score P < 10-6, in which case P values are from a Firth test with no genomic control. Novel loci are underlined.
Intergenic
121
GSTCD123
GSTCD124
UK Brain Expression Consortium
John A Hardy1, Michael E Weale2, Mina Ryten1,2, Colin Smith3, Robert Walker3, Juan Botía1,2, Jana Vandrocova1,2, Sebastian Guelfi1,2, Karishma D’Sa1,2, Mar Matarin1, Vibin Varghese2, Daniah Trabzuni1, Adaikalavan Ramasamy1,2,4 and Paola Forabosco2,5.
1Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK; 2
Department of Medical & Molecular Genetics, King's College London SE1 9RT, UK;
3Department of Pathology, The University of Edinburgh, Wilkie Building, Teviot Place, Edinburgh EH8 9AG,
UK;
4Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK;
5Istituto di Ricerca Genetica e Biomedica, Cittadella Universitaria di Cagliari, 09042 Monserrato, Sardinia,
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OxGSK Consortium
Jason Z Liu1, Federica Tozzi2, Dawn M Waterworth3, Sreekumar G Pillai3, Pierandrea Muglia2, Lefkos Middleton4, Wade Berrettini5, Christopher W Knouff6, Xin Yuan3, Gérard Waeber7,8, Peter Vollenweider7, 8, Martin Preisig7,9, Nicholas J Wareham10, Jing Hua Zhao10, Ruth J F Loos10, Inês Barroso11, Kay-Tee Khaw12, Scott Grundy13, Philip Barter14, Robert Mahley15,16, Antero Kesaniemi17,18, Ruth McPherson19, John B Vincent20, John Strauss20, James L Kennedy20, Anne Farmer21, Peter McGuffin21, Richard Day22, Keith Matthews22, Per Bakke23, Amund Gulsvik23, Susanne Lucae24, Marcus Ising24, Tanja Brueckl24, Sonja Horstmann24, H-Erich Wichmann25,26,27, Rajesh Rawal25, Norbert Dahmen28, Claudia Lamina25,29, Ozren Polasek30, Lina Zgaga31, Jennifer Huffman32, Susan Campbell32, Jaspal Kooner33, John C Chambers34, Mary Susan Burnett35, Joseph M Devaney35, Augusto D Pichard35, Kenneth M Kent35, Lowell Satler35, Joseph M Lindsay35, Ron Waksman35, Stephen Epstein35, James F Wilson31, Sarah H Wild31, Harry Campbell31, Veronique Vitart32, Muredach P Reilly36, 37, Mingyao Li38, Liming Qu38, Robert Wilensky36, William Matthai36, Hakon H Hakonarson39, Daniel J Rader36, 37, David Ellinghaus40, Wolfgang Lieb41, Andre Franke40, Manuela Uda42, Antonio Terracciano43, Xiangjun Xiao44, Fabio Busonero42, Paul Scheet44, David Schlessinger43, David St Clair45, Dan Rujescu46, Gonçalo R Abecasis47, Hans Jörgen Grabe48, Alexander Teumer49, Henry Völzke50, Astrid Petersmann51, Ulrich John52, Igor Rudan53,31, Caroline Hayward32, Alan F Wright32, Ivana Kolcic30, Benjamin J Wright54, John R Thompson54, Anthony J Balmforth55, Alistair S Hall55, Nilesh J Samani56, Carl A Anderson11, Tariq Ahmad57, Christopher G Mathew58, Miles Parkes59, Jack Satsangi60, Mark Caulfield61, Patricia B Munroe61, Martin Farrall62, Anna Dominiczak63, Jane Worthington64, Wendy Thomson64, Steve Eyre64, Anne Barton64, The Wellcome Trust Case Control Consortium65, Vincent Mooser3, Clyde Francks66, 67, Jonathan Marchini1
1. Department of Statistics, University of Oxford, Oxford, UK. 2. Genetics Division, GlaxoSmithKline, Verona, Italy.
3. Genetics Division, GlaxoSmithKline, Upper Merion, Pennsylvania, USA. 4. Division of Neurosciences and Mental Health, Imperial College London, UK.
5. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
6. Genetics Division, GlaxoSmithKline, Research Triangle Park, North Carolina, USA. 7. Faculty of Biology and Medicine, University of Lausanne, 1011 Lausanne, Switzerland.
8. Department of Internal Medicine, University Hospital of Lausanne, 1011 Lausanne, Switzerland. 9. Department of Psychiatry, University Hospital of Lausanne, 1011 Lausanne, Switzerland. 10. Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK. 11. Wellcome Trust Sanger Institute, Hinxton, UK.
12. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
13. Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 14. The Heart Research Institute, Sydney, New South Wales, Australia.
15. Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California, USA. 16. American Hospital, Istanbul, Turkey.
17. Department of Internal Medicine, University of Oulu, Oulu, Finland. 18. Biocenter Oulu, University of Oulu, Oulu, Finland.
19. Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 20. Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
21. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
22. Center for Neuroscience, Division of Medical Sciences, University of Dundee, Dundee, UK. 23. Institute of Medicine, University of Bergen, Bergen, Norway.
24. Max Planck Institute of Psychiatry, Munich, Germany.
25. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
26. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-MaximiliansUniversität, Munich, Germany.
27. Klinikum Grosshadern, Munich, Germany.
28. Psychiatrische Klinik und Poliklinik University of Mainz, Mainz, Germany.
29. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
30. School of Public Health, School of Medicine, University of Zagreb, Croatia. 31. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
32. Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh, UK. 33. National Heart and Lung Institute, Imperial College London, London, UK.
126
35. Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington DC, USA.36. The Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
37. The Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
38. Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
39. The Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 40. Institute of Clinical Molecular Biology, ChristianAlbrechts-University of Kiel, Kiel, Germany.
41. Institute of Epidemiology and Biobank Popgen, Christian-Albrechts-University of Kiel, Kiel, Germany. 42. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Monserrato, Cagliari, Italy.
43. National Institute on Aging, Baltimore, Maryland, USA.
44. Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 45. Department of Mental Health, University of Aberdeen, Aberdeen, UK.
46. Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians- University, Munich, Germany.
47. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
48. Department of Psychiatry and Psychotherapy, University of Greifswald, Greifswald, Germany.
49. Interfacultary Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
50. Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
51. Institute of Clinical Chemistry and Laboratory Medicine, University of Greifswald, Greifswald, Germany. 52. Department of Social Medicine and Epidemiology, University of Greifswald, Greifswald, Germany. 53. Croatian Centre for Global Health, University of Split, Split, Croatia.
54. Department of Health Sciences, University of Leicester, Leicester, UK.
55. Mulitdisciplinary Cardiovascular Research Centre (MCRC), Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds, UK.
56. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK. 57. Peninsula College of Medicine and Dentistry, Exeter, UK.
58. Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, London, UK.
59. Gastroenterology Research Unit, Addenbrooke’s Hospital, Cambridge, UK.
60. Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK.
61. Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
62. Department of Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK.
63. British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow, UK.
64. Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, Manchester Academic Health Sciences Centre, Stopford Building, Oxford Rd, Manchester, M13 9PT, UK.
65. A full list of members is provided in the Supplementary Material.
66. Language & Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. 67. Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
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Appendix 1:
UK Biobank Unique Identifiers (UDIs) used to select individuals for UK BiLEVE.
Variable UK Biobank
Unique Data Identifier
Notes
Ethnicity 21000
FEV1 3063
FVC 3062
Acceptability of each blow result 3061 Used for determining whether met ATS/ERS criteria.
Spirometry Method 23
Age at recruitment 21003
Sex 31
Standing Height 50
Current tobacco smoking 1239 Yes, on most or all days / Only Occasionally / No / Prefer not to answer.
Past tobacco smoking 1249 Smoked on most or all days / Smoked occasionally / Just tried once or twice / I have never smoked / Prefer not to answer.
Type of tobacco currently smoked (current smokers)
3446 Manufactured cigarettes / Hand-rolled cigarettes / Cigars or pipes / Prefer not to answer.
Type of tobacco previously smoked (former smokers)
2877 Manufactured cigarettes / Hand-rolled cigarettes / Cigars or pipes / Prefer not to answer.
Previously smoked cigarettes on most/all days (current pipe/cigar smokers)
5959 Asked if answered “Yes, on most or all days” to 1239 and “Cigars or pipes” to 3446.
Age started smoking (current smokers) 3436 Age started smoking (former smokers) 2867 Age stopped smoking (former smokers) 2897 Age stopped smoking cigarettes
(current pipe/cigar smokers)
6194 Number of cigarettes smoked daily
(current smokers)
3456 Number of cigarettes previously smoked daily
(former smokers)
2887 Number of cigarettes previously smoked daily
(current pipe/cigar smokers)
6183 Ever stopped smoking for 6+ months 2907 Blood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor
6152 Excluded from “healthy never smokers” if answered bronchitis, emphysema or asthma.
Wheeze or whistling in the chest in last year 2316 Excluded from “healthy never smokers” if answered yes/don’t know or prefer not to answer.
Self-reported non-cancer illness 20002 Excluded from “healthy never smokers” if answered any of the following: asthma; copd; emphysema; chronic bronchitis; bronchiectasis; interstitial lung disease; asbestosis; pulmonary fibrosis; fibrosing /unspecified alveolitis; respiratory failure; pleurisy; spontaneous/recurrent pneumothorax; other respiratory problems