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Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium
  1. Richard W Morris1,2,
  2. Amy E Taylor3,4,
  3. Meg E Fluharty3,4,
  4. Johan H Bjørngaard5,6,
  5. Bjørn Olav Åsvold5,7,
  6. Maiken Elvestad Gabrielsen8,
  7. Archie Campbell9,
  8. Riccardo Marioni9,10,11,
  9. Meena Kumari12,
  10. Tellervo Korhonen13,14,15,
  11. Satu Männistö13,
  12. Pedro Marques-Vidal16,
  13. Marika Kaakinen17,18,
  14. Alana Cavadino19,20,
  15. Iris Postmus21,22,
  16. Lise Lotte N Husemoen23,
  17. Tea Skaaby23,
  18. Tarun Veer Singh Ahluwalia24,25,26,
  19. Jorien L Treur27,
  20. Gonneke Willemsen27,
  21. Caroline Dale28,
  22. S Goya Wannamethee2,
  23. Jari Lahti29,30,
  24. Aarno Palotie31,32,33,
  25. Katri Räikkönen29,
  26. Alex McConnachie34,
  27. Sandosh Padmanabhan35,
  28. Andrew Wong36,
  29. Christine Dalgård37,
  30. Lavinia Paternoster1,3,
  31. Yoav Ben-Shlomo1,
  32. Jessica Tyrrell38,39,
  33. John Horwood40,
  34. David M Fergusson40,
  35. Martin A Kennedy41,
  36. Ellen A Nohr42,
  37. Lene Christiansen43,
  38. Kirsten Ohm Kyvik37,
  39. Diana Kuh36,
  40. Graham Watt44,
  41. Johan G Eriksson15,30,45,46,47,
  42. Peter H Whincup48,
  43. Jacqueline M Vink27,
  44. Dorret I Boomsma27,
  45. George Davey Smith1,3,
  46. Debbie Lawlor1,3,
  47. Allan Linneberg23,49,50,
  48. Ian Ford34,
  49. J Wouter Jukema51,52,53,
  50. Chris Power20,
  51. Elina Hyppönen20,54,55,
  52. Marjo-Riitta Jarvelin17,18,56,57,58,
  53. Martin Preisig59,
  54. Katja Borodulin15,
  55. Jaakko Kaprio13,15,60,
  56. Mika Kivimaki61,
  57. Blair H Smith62,
  58. Caroline Hayward63,
  59. Pål R Romundstad5,
  60. Thorkild I A Sørensen3,24,64,
  61. Marcus R Munafò3,4,
  62. Naveed Sattar65
  1. 1School of Social and Community Medicine, University of Bristol, Bristol, UK
  2. 2Department of Primary Care and Population Health, UCL, London, UK
  3. 3MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK
  4. 4UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK
  5. 5Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  6. 6Forensic Department, Research Centre Bröset, St Olav's University Hospital Trondheim, Trondheim, Norway
  7. 7Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  8. 8Department of Laboratory Medicine, Children's and Women's Health, The Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  9. 9Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  10. 10Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  11. 11Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia
  12. 12Institute for Social and Economic Research, University of Essex, Colchester, UK
  13. 13Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
  14. 14Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
  15. 15National Institute for Health and Welfare, Helsinki, Finland
  16. 16Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
  17. 17Institute of Health Sciences, University of Oulu, Oulu, Finland
  18. 18Biocenter Oulu, University of Oulu, Oulu, Finland
  19. 19Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  20. 20Population, Policy and Practice, UCL Institute of Child Health, University College London, UK
  21. 21Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
  22. 22Netherlands Consortium of Healthy Ageing, Leiden, The Netherlands
  23. 23Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark
  24. 24Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  25. 25Steno Diabetes Center, Gentofte, Denmark
  26. 26COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  27. 27Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands
  28. 28Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
  29. 29Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
  30. 30Folkhälsan Research Centre, Helsinki, Finland
  31. 31Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
  32. 32Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
  33. 33The Medical and Population Genomics Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  34. 34Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
  35. 35Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  36. 36MRC Unit for Lifelong Health and Ageing at UCL, London, UK
  37. 37Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark
  38. 38European Centre for Environment and Human Health, University of Exeter Medical School, Truro, UK
  39. 39Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK
  40. 40Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
  41. 41Department of Pathology, University of Otago, Christchurch, New Zealand
  42. 42Institute for Clinical Research, University of Southern Denmark, Odense, Denmark
  43. 43Department of Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Denmark
  44. 44University of Glasgow, Glasgow, UK
  45. 45Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
  46. 46Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland
  47. 47Vasa Central Hospital, Vasa, Finland
  48. 48Population Health Research Institute, St George's University of London, London, UK
  49. 49Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark.
  50. 50Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  51. 51Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
  52. 52Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands
  53. 53Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  54. 54Centre for Population Health Research, School of Health Sciences and Sansom Institute of Health Research, University of South Australia, Adelaide, Australia
  55. 55South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  56. 56Unit of Primary Care, Oulu University Hospital, Oulu, Finland
  57. 57Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland
  58. 58Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
  59. 59Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
  60. 60Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
  61. 61Department of Epidemiology and Public Health, University College London, London, UK
  62. 62Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  63. 63Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  64. 64Institute of Preventive Medicine, Bispebjerg and Frederikberg Hospitals, The Capital Region, Copenhagen, Denmark
  65. 65Faculty of Medicine, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK
  1. Correspondence to Professor Richard W Morris; richard.morris{at}bristol.ac.uk

Abstract

Objectives To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.

Design Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.

Participants 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).

Primary outcome measures Waist and hip circumferences, and waist-hip ratio.

Results The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by −0.40% (95% CI −0.57% to −0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being −0.31% (95% CI −0.42% to −0.19), −0.08% (−0.19% to 0.03%) and −0.74% (−0.96% to −0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (−0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (−0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.

Conclusions For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.

  • EPIDEMIOLOGY
  • GENETICS

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