Body mass index and all cause mortality in HUNT and UK Biobank studies: linear and non-linear mendelian randomisation analyses
Sun, Yi-Qian; Burgess, Stephen; Staley, James R.; Wood, Angela M.; Bell, Steven; Kaptoge, Stephen; Guo, Qi; Bolton, Thomas R.; Mason, Amy M; Butterworth, Adam S.; Di Angelantonio, Emanuele; Vie, Gunnhild Åberge; Bjørngaard, Johan Håkon; Kinge, Jonas Minet; Chen, Yue; Mai, Xiao-Mei
Journal article, Peer reviewed
Published version
Åpne
Permanent lenke
http://hdl.handle.net/11250/2595806Utgivelsesdato
2019Metadata
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Originalversjon
10.1136/bmj.l1042Sammendrag
Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality.
Design Linear and non-linear mendelian randomisation analyses.
Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom).
Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank.
Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality.
Results 12 015 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.
Conclusions The 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.