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.
OBJECTIVE
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.


METHODS
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.


METHODS
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).


METHODS
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.
School of Social and Community Medicine, University of Bristol, Bristol, UK Department of Primary Care and Population Health, UCL, London, UK.
Richard W
RW
Morris
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK.
Amy E
AE
Taylor
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK.
Meg E
ME
Fluharty
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Forensic Department, Research Centre Bröset, St Olav's University Hospital Trondheim, Trondheim, Norway.
Johan H
JH
Bjørngaard
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Bjørn Olav
BO
Åsvold
Department of Laboratory Medicine, Children's and Women's Health, The Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Maiken
M
Elvestad Gabrielsen
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Archie
A
Campbell
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Riccardo
R
Marioni
Institute for Social and Economic Research, University of Essex, Colchester, UK.
Meena
M
Kumari
Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland National Institute for Health and Welfare, Helsinki, Finland.
Tellervo
T
Korhonen
Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland.
Satu
S
Männistö
Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Pedro
P
Marques-Vidal
Institute of Health Sciences, University of Oulu, Oulu, Finland Biocenter Oulu, University of Oulu, Oulu, Finland.
Marika
M
Kaakinen
Centre 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 Population, Policy and Practice, UCL Institute of Child Health, University College London, UK.
Alana
A
Cavadino
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium of Healthy Ageing, Leiden, The Netherlands.
Iris
I
Postmus
Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark.
Lise Lotte N
LL
Husemoen
Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark.
Tea
T
Skaaby
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Steno Diabetes Center, Gentofte, Denmark COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Tarun Veer Singh
TV
Ahluwalia
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
Jorien L
JL
Treur
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
Gonneke
G
Willemsen
Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Caroline
C
Dale
Department of Primary Care and Population Health, UCL, London, UK.
S Goya
SG
Wannamethee
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland Folkhälsan Research Centre, Helsinki, Finland.
Jari
J
Lahti
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland The Medical and Population Genomics Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Aarno
A
Palotie
Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Katri
K
Räikkönen
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Alex
A
McConnachie
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Sandosh
S
Padmanabhan
MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Andrew
A
Wong
Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Christine
C
Dalgård
School of Social and Community Medicine, University of Bristol, Bristol, UK MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK.
Lavinia
L
Paternoster
School of Social and Community Medicine, University of Bristol, Bristol, UK.
Yoav
Y
Ben-Shlomo
European Centre for Environment and Human Health, University of Exeter Medical School, Truro, UK Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
Jessica
J
Tyrrell
Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
John
J
Horwood
Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
David M
DM
Fergusson
Department of Pathology, University of Otago, Christchurch, New Zealand.
Martin A
MA
Kennedy
Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
Ellen A
EA
Nohr
Department of Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Denmark.
Lene
L
Christiansen
Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
Kirsten Ohm
KO
Kyvik
MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Diana
D
Kuh
University of Glasgow, Glasgow, UK.
Graham
G
Watt
National Institute for Health and Welfare, Helsinki, Finland Folkhälsan Research Centre, Helsinki, Finland Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland Vasa Central Hospital, Vasa, Finland.
Johan G
JG
Eriksson
Population Health Research Institute, St George's University of London, London, UK.
Peter H
PH
Whincup
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
Jacqueline M
JM
Vink
Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
Dorret I
DI
Boomsma
School of Social and Community Medicine, University of Bristol, Bristol, UK MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK.
George
G
Davey Smith
School of Social and Community Medicine, University of Bristol, Bristol, UK MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK.
Debbie
D
Lawlor
Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark Department of Clinical Experimental Research, Glostrup University Hospital, Glostrup, Denmark. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Allan
A
Linneberg
Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Ian
I
Ford
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
J Wouter
JW
Jukema
Population, Policy and Practice, UCL Institute of Child Health, University College London, UK.
Chris
C
Power
Population, Policy and Practice, UCL Institute of Child Health, University College London, UK Centre for Population Health Research, School of Health Sciences and Sansom Institute of Health Research, University of South Australia, Adelaide, Australia South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Elina
E
Hyppönen
Institute of Health Sciences, University of Oulu, Oulu, Finland Biocenter Oulu, University of Oulu, Oulu, Finland Unit of Primary Care, Oulu University Hospital, Oulu, Finland Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Marjo-Riitta
MR
Jarvelin
Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Martin
M
Preisig
National Institute for Health and Welfare, Helsinki, Finland.
Katja
K
Borodulin
Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland National Institute for Health and Welfare, Helsinki, Finland Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Jaakko
J
Kaprio
Department of Epidemiology and Public Health, University College London, London, UK.
Mika
M
Kivimaki
Division of Population Health Sciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Blair H
BH
Smith
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Caroline
C
Hayward
Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Pål R
PR
Romundstad
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Institute of Preventive Medicine, Bispebjerg and Frederikberg Hospitals, The Capital Region, Copenhagen, Denmark.
Thorkild I A
TI
Sørensen
MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, University of Bristol, Bristol, UK UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK.
Marcus R
MR
Munafò
Faculty of Medicine, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK.
Naveed
N
Sattar
D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D055815:Young Adult
EPIDEMIOLOGY; GENETICS