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

Richard W Morris, Amy E Taylor, Meg E Fluharty, Johan H Bjørngaard, Bjørn Olav Åsvold, Maiken Elvestad Gabrielsen, Archie Campbell, Riccardo Marioni, Meena Kumari, Tellervo Korhonen, Satu Männistö, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Lise Lotte N Husemoen, Tea Skaaby, Tarun Veer Singh Ahluwalia, Jorien L Treur, Gonneke WillemsenCaroline Dale, S Goya Wannamethee, Jari Lahti, Aarno Palotie, Katri Räikkönen, Alex McConnachie, Sandosh Padmanabhan, Andrew Wong, Christine Dalgård, Lavinia Paternoster, Yoav Ben-Shlomo, Jessica Tyrrell, John Horwood, David M Fergusson, Martin A Kennedy, Ellen A Nohr, Lene Christiansen, Kirsten Ohm Kyvik, Diana Kuh, Graham Watt, Johan G Eriksson, Peter H Whincup, Jacqueline M Vink, Dorret I Boomsma, George Davey Smith, Debbie Lawlor, Allan Linneberg, Ian Ford, J Wouter Jukema, Chris Power, Elina Hyppönen, Marjo-Riitta Jarvelin, Martin Preisig, Katja Borodulin, Jaakko Kaprio, Mika Kivimaki, Blair H Smith, Caroline Hayward, Pål R Romundstad, Thorkild I A Sørensen, Marcus R Munafò, Naveed Sattar

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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.

Original languageEnglish
Article numbere008808
JournalBMJ Open
Volume5
Issue number8
ISSN2044-6055
DOIs
Publication statusPublished - Aug 2015

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Mendelian Randomization Analysis
Adiposity
Meta-Analysis
Smoking
Alcohols
Hip
Research
Body Mass Index
Alleles
Proxy
Random Allocation
Outcome Assessment (Health Care)
Weights and Measures

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Morris, R. W., Taylor, A. E., Fluharty, M. E., Bjørngaard, J. H., Åsvold, B. O., Elvestad Gabrielsen, M., ... Sattar, N. (2015). 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. BMJ Open, 5(8), [e008808]. https://doi.org/10.1136/bmjopen-2015-008808
Morris, Richard W ; Taylor, Amy E ; Fluharty, Meg E ; Bjørngaard, Johan H ; Åsvold, Bjørn Olav ; Elvestad Gabrielsen, Maiken ; Campbell, Archie ; Marioni, Riccardo ; Kumari, Meena ; Korhonen, Tellervo ; Männistö, Satu ; Marques-Vidal, Pedro ; Kaakinen, Marika ; Cavadino, Alana ; Postmus, Iris ; Husemoen, Lise Lotte N ; Skaaby, Tea ; Ahluwalia, Tarun Veer Singh ; Treur, Jorien L ; Willemsen, Gonneke ; Dale, Caroline ; Wannamethee, S Goya ; Lahti, Jari ; Palotie, Aarno ; Räikkönen, Katri ; McConnachie, Alex ; Padmanabhan, Sandosh ; Wong, Andrew ; Dalgård, Christine ; Paternoster, Lavinia ; Ben-Shlomo, Yoav ; Tyrrell, Jessica ; Horwood, John ; Fergusson, David M ; Kennedy, Martin A ; Nohr, Ellen A ; Christiansen, Lene ; Kyvik, Kirsten Ohm ; Kuh, Diana ; Watt, Graham ; Eriksson, Johan G ; Whincup, Peter H ; Vink, Jacqueline M ; Boomsma, Dorret I ; Davey Smith, George ; Lawlor, Debbie ; Linneberg, Allan ; Ford, Ian ; Jukema, J Wouter ; Power, Chris ; Hyppönen, Elina ; Jarvelin, Marjo-Riitta ; Preisig, Martin ; Borodulin, Katja ; Kaprio, Jaakko ; Kivimaki, Mika ; Smith, Blair H ; Hayward, Caroline ; Romundstad, Pål R ; Sørensen, Thorkild I A ; Munafò, Marcus R ; Sattar, Naveed. / 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. In: BMJ Open. 2015 ; Vol. 5, No. 8.
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title = "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",
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.",
author = "Morris, {Richard W} and Taylor, {Amy E} and Fluharty, {Meg E} and Bj{\o}rngaard, {Johan H} and {\AA}svold, {Bj{\o}rn Olav} and {Elvestad Gabrielsen}, Maiken and Archie Campbell and Riccardo Marioni and Meena Kumari and Tellervo Korhonen and Satu M{\"a}nnist{\"o} and Pedro Marques-Vidal and Marika Kaakinen and Alana Cavadino and Iris Postmus and Husemoen, {Lise Lotte N} and Tea Skaaby and Ahluwalia, {Tarun Veer Singh} and Treur, {Jorien L} and Gonneke Willemsen and Caroline Dale and Wannamethee, {S Goya} and Jari Lahti and Aarno Palotie and Katri R{\"a}ikk{\"o}nen and Alex McConnachie and Sandosh Padmanabhan and Andrew Wong and Christine Dalg{\aa}rd and Lavinia Paternoster and Yoav Ben-Shlomo and Jessica Tyrrell and John Horwood and Fergusson, {David M} and Kennedy, {Martin A} and Nohr, {Ellen A} and Lene Christiansen and Kyvik, {Kirsten Ohm} and Diana Kuh and Graham Watt and Eriksson, {Johan G} and Whincup, {Peter H} and Vink, {Jacqueline M} and Boomsma, {Dorret I} and {Davey Smith}, George and Debbie Lawlor and Allan Linneberg and Ian Ford and Jukema, {J Wouter} and Chris Power and Elina Hypp{\"o}nen and Marjo-Riitta Jarvelin and Martin Preisig and Katja Borodulin and Jaakko Kaprio and Mika Kivimaki and Smith, {Blair H} and Caroline Hayward and Romundstad, {P{\aa}l R} and S{\o}rensen, {Thorkild I A} and Munaf{\`o}, {Marcus R} and Naveed Sattar",
note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",
year = "2015",
month = "8",
doi = "10.1136/bmjopen-2015-008808",
language = "English",
volume = "5",
journal = "B M J Open",
issn = "2044-6055",
publisher = "BMJ Group",
number = "8",

}

Morris, RW, Taylor, AE, Fluharty, ME, Bjørngaard, JH, Åsvold, BO, Elvestad Gabrielsen, M, Campbell, A, Marioni, R, Kumari, M, Korhonen, T, Männistö, S, Marques-Vidal, P, Kaakinen, M, Cavadino, A, Postmus, I, Husemoen, LLN, Skaaby, T, Ahluwalia, TVS, Treur, JL, Willemsen, G, Dale, C, Wannamethee, SG, Lahti, J, Palotie, A, Räikkönen, K, McConnachie, A, Padmanabhan, S, Wong, A, Dalgård, C, Paternoster, L, Ben-Shlomo, Y, Tyrrell, J, Horwood, J, Fergusson, DM, Kennedy, MA, Nohr, EA, Christiansen, L, Kyvik, KO, Kuh, D, Watt, G, Eriksson, JG, Whincup, PH, Vink, JM, Boomsma, DI, Davey Smith, G, Lawlor, D, Linneberg, A, Ford, I, Jukema, JW, Power, C, Hyppönen, E, Jarvelin, M-R, Preisig, M, Borodulin, K, Kaprio, J, Kivimaki, M, Smith, BH, Hayward, C, Romundstad, PR, Sørensen, TIA, Munafò, MR & Sattar, N 2015, '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', BMJ Open, vol. 5, no. 8, e008808. https://doi.org/10.1136/bmjopen-2015-008808

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. / Morris, Richard W; Taylor, Amy E; Fluharty, Meg E; Bjørngaard, Johan H; Åsvold, Bjørn Olav; Elvestad Gabrielsen, Maiken; Campbell, Archie; Marioni, Riccardo; Kumari, Meena; Korhonen, Tellervo; Männistö, Satu; Marques-Vidal, Pedro; Kaakinen, Marika; Cavadino, Alana; Postmus, Iris; Husemoen, Lise Lotte N; Skaaby, Tea; Ahluwalia, Tarun Veer Singh; Treur, Jorien L; Willemsen, Gonneke; Dale, Caroline; Wannamethee, S Goya; Lahti, Jari; Palotie, Aarno; Räikkönen, Katri; McConnachie, Alex; Padmanabhan, Sandosh; Wong, Andrew; Dalgård, Christine; Paternoster, Lavinia; Ben-Shlomo, Yoav; Tyrrell, Jessica; Horwood, John; Fergusson, David M; Kennedy, Martin A; Nohr, Ellen A; Christiansen, Lene; Kyvik, Kirsten Ohm; Kuh, Diana; Watt, Graham; Eriksson, Johan G; Whincup, Peter H; Vink, Jacqueline M; Boomsma, Dorret I; Davey Smith, George; Lawlor, Debbie; Linneberg, Allan; Ford, Ian; Jukema, J Wouter; Power, Chris; Hyppönen, Elina; Jarvelin, Marjo-Riitta; Preisig, Martin; Borodulin, Katja; Kaprio, Jaakko; Kivimaki, Mika; Smith, Blair H; Hayward, Caroline; Romundstad, Pål R; Sørensen, Thorkild I A; Munafò, Marcus R; Sattar, Naveed.

In: BMJ Open, Vol. 5, No. 8, e008808, 08.2015.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Heavier smoking may lead to a relative increase in waist circumference

T2 - evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium

AU - Morris, Richard W

AU - Taylor, Amy E

AU - Fluharty, Meg E

AU - Bjørngaard, Johan H

AU - Åsvold, Bjørn Olav

AU - Elvestad Gabrielsen, Maiken

AU - Campbell, Archie

AU - Marioni, Riccardo

AU - Kumari, Meena

AU - Korhonen, Tellervo

AU - Männistö, Satu

AU - Marques-Vidal, Pedro

AU - Kaakinen, Marika

AU - Cavadino, Alana

AU - Postmus, Iris

AU - Husemoen, Lise Lotte N

AU - Skaaby, Tea

AU - Ahluwalia, Tarun Veer Singh

AU - Treur, Jorien L

AU - Willemsen, Gonneke

AU - Dale, Caroline

AU - Wannamethee, S Goya

AU - Lahti, Jari

AU - Palotie, Aarno

AU - Räikkönen, Katri

AU - McConnachie, Alex

AU - Padmanabhan, Sandosh

AU - Wong, Andrew

AU - Dalgård, Christine

AU - Paternoster, Lavinia

AU - Ben-Shlomo, Yoav

AU - Tyrrell, Jessica

AU - Horwood, John

AU - Fergusson, David M

AU - Kennedy, Martin A

AU - Nohr, Ellen A

AU - Christiansen, Lene

AU - Kyvik, Kirsten Ohm

AU - Kuh, Diana

AU - Watt, Graham

AU - Eriksson, Johan G

AU - Whincup, Peter H

AU - Vink, Jacqueline M

AU - Boomsma, Dorret I

AU - Davey Smith, George

AU - Lawlor, Debbie

AU - Linneberg, Allan

AU - Ford, Ian

AU - Jukema, J Wouter

AU - Power, Chris

AU - Hyppönen, Elina

AU - Jarvelin, Marjo-Riitta

AU - Preisig, Martin

AU - Borodulin, Katja

AU - Kaprio, Jaakko

AU - Kivimaki, Mika

AU - Smith, Blair H

AU - Hayward, Caroline

AU - Romundstad, Pål R

AU - Sørensen, Thorkild I A

AU - Munafò, Marcus R

AU - Sattar, Naveed

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

U2 - 10.1136/bmjopen-2015-008808

DO - 10.1136/bmjopen-2015-008808

M3 - Journal article

C2 - 26264275

VL - 5

JO - B M J Open

JF - B M J Open

SN - 2044-6055

IS - 8

M1 - e008808

ER -