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, RW; Taylor, AE; Fluharty, ME; Bjørngaard, JH; Åsvold, BO; Elvestad Gabrielsen, M; Campbell, A; Marioni, R; Kumari, M; Korhonen, T; +52 more...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; Preisig, M; Borodulin, K; Kaprio, J; Kivimaki, M; Smith, BH; Hayward, C; Romundstad, PR; Sørensen, TI; Munafò, MR; Sattar, N and (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.