| Title: | Body mass index and all cause mortality in HUNT and UK Biobank studies: linear and non-linear mendelian randomisation analyses |
| Journal: | The BMJ |
| Published: | 26 Mar 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30957776/ |
| DOI: | https://doi.org/10.1136/bmj.l1042 |
| URL: | https://www.bmj.com/content/bmj/364/bmj.l1042.full.pdf |
| Citations: | 158 (43 in last 2 years) as of 8 Aug 2024 |
Publication 4381
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Abstract
EDITOR'S NOTE: Please see the Editor's Note (doi: https://doi.org/10.1136/bmj.l1042) on Methodological Criticism and an Updated Analysis</p>
OBJECTIVE: To investigate the shape of the causal relation between body mass index (BMI) and mortality.</p>
DESIGN: Linear and non-linear mendelian randomisation analyses.</p>
SETTING: Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom).</p>
PARTICIPANTS: Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank.</p>
MAIN OUTCOME MEASURES: All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality.</p>
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.</p>
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.</p>
16 Authors
- 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
- Xiao-Mei Mai
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