• Yi-Qian Sun, Stephen Burgess, James R Staley, Angela M Wood, Steven Bell, Stephen K Kaptoge, Qi Guo, Thomas R Bolton, Amy M Mason, Adam S Butterworth, Emanuele Di Angelantonio, Gunnhild Å Vie, Johan H Bjørngaard, Jonas Minet Kinge, Yue Chen, and Xiao-Mei Mai.
• Department of Clinical and Molecular Medicine (IKOM), NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
• BMJ. 2019 Mar 26; 364: l1042.

ObjectiveTo investigate the shape of the causal relation between body mass index (BMI) and mortality.DesignLinear and non-linear mendelian randomisation analyses.SettingNord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom).ParticipantsMiddle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank.Main Outcome MeasuresAll cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality.Results12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI <18.5) and a 14% (-1% to 27%) lower risk in low normal weight participants (BMI 18.5-19.9). Non-linear mendelian randomisation indicated a J shaped relation between genetically predicted BMI and the risk of all cause mortality, with the lowest risk at a BMI of around 22-25 for the overall sample. Subgroup analyses by smoking status, however, suggested an always-increasing relation of BMI with mortality in never smokers and a J shaped relation in ever smokers.ConclusionsThe previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. An increased risk of mortality for being underweight was only evident in ever smokers.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.

23 keywords...

hide…