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; +52 more... 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 Willemsen; Caroline 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 IA Sørensen; Marcus R Munafò; Naveed Sattar; (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-. ISSN 2044-6055 DOI: 10.1136/bmjopen-2015-008808

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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.