| Title: | Body mass index and all-cause mortality in HUNT and UK biobank studies: revised non-linear Mendelian randomisation analyses |
| Journal: | BMJ Open |
| Published: | 15 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38749693/ |
| DOI: | https://doi.org/10.1136/bmjopen-2023-081399 |
| URL: | https://bmjopen.bmj.com/content/bmjopen/14/5/e081399.full.pdf |
| Citations: | 1 (1 in last 2 years) as of 8 Aug 2024 |
Publication 12078
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Abstract
OBJECTIVES: To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.</p>
DESIGN: Mendelian randomisation analyses of two prospective population-based cohorts.</p>
SETTING: Individuals of European ancestries living in Norway or the UK.</p>
PARTICIPANTS: 56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation.</p>
OUTCOMES: All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer).</p>
RESULTS: A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m2. However, the 'constant genetic effect' assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m2. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m2, for cardiovascular mortality above 24 kg/m2, for cancer mortality above 30 kg/m2 and for non-cardiovascular non-cancer mortality above 26 kg/m2. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men.</p>
CONCLUSION: This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m2. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m2.</p>
6 Authors
- Stephen Burgess
- Yi-Qian Sun
- Ang Zhou
- Christopher Buck
- Amy M Mason
- Xiao-Mei Mai
1 Application
| Application ID | Title |
|---|---|
| 7439 | Comparissons of measures of adiposity including body-mass index, waist-circumference, waist-to-hip ratio, and percentage body fat mass |
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