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
Authors: 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 
Published: August 2015

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 theCHRNA5-CHRNA3-CHRNB4gene 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.