The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality studyBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b5043 (Published 23 December 2009) Cite this as: BMJ 2009;339:b5043
- George Davey Smith, professor of clinical epidemiology 1,
- Jonathan AC Sterne, professor of medical statistics and epidemiology2,
- Abigail Fraser, Medical Research Council postdoctoral fellow in health services research and health of the public1,
- Per Tynelius, statistician 3,
- Debbie A Lawlor, professor of epidemiology 1,
- Finn Rasmussen, professor 3
- 1Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol, BS8 2BN
- 2Department of Social Medicine, University of Bristol, Bristol, BS8 2PR
- 3Department of Public Health Sciences, Karolinska Institute, S-171 76 Stockholm, Sweden
- Correspondence to F Rasmussen
- Accepted 1 October 2009
Objectives To obtain valid estimates of the association between body mass index (BMI) and mortality by using offspring BMI as an instrumental variable for own BMI.
Design Cohort study based on record linkage, with 50 years of follow-up for mortality. Associations of offspring BMI with all cause and cause specific maternal and paternal mortality were estimated as hazard ratios per standard deviation of offspring BMI.
Setting A large intergenerational prospective population based database covering the general population of Sweden.
Participants More than one million Swedish parent-son pairs.
Results The final dataset analysed contained information on 1 018 012 mother-son pairs (122 677 maternal deaths) and 1 004 617 father-son pairs (242 126 paternal deaths). For some causes of death, the patterns of associations between offspring BMI and mortality were similar to those seen for own BMI and mortality in previous studies. Parental mortality from diabetes, coronary heart disease, and kidney cancer had the strongest positive associations with offspring BMI (for example, hazard ratio (HR) for coronary heart disease per standard deviation increase in offspring BMI for mothers 1.15, 95% CI 1.14 to 1.17 and for fathers 1.10, 1.09 to 1.11). However, in contrast to the inverse association of own BMI with lung cancer and respiratory disease mortality seen in other studies, there was a positive association between offspring BMI and lung cancer mortality in mothers (1.12, 1.09 to 1.15) and fathers (1.03, 1.02 to 1.05) and between offspring BMI and respiratory mortality in mothers (1.05, 1.02 to 1.08) and fathers (1.02, 1.00 to 1.04). Associations of own BMI and offspring BMI with all cause, cardiovascular disease related, and non-cardiovascular disease related mortality were compared in a subset of father-son pairs (n=72 815). When offspring BMI was used as an instrumental variable for paternal BMI, the causal association between BMI and paternal cardiovascular disease mortality (HR per standard deviation of BMI 1.82, 95% CI 1.17 to 2.83) was stronger than that indicated by the directly observed association between own BMI and cardiovascular disease mortality (1.45, 1.31 to 1.61).
Conclusions Use of offspring BMI as a predictor of own BMI, a technique that avoids problems of reverse causality, suggests that positive associations of BMI with all cause and cardiovascular mortality may be underestimated in conventional observational studies. Use of offspring BMI instead of own BMI in analyses of respiratory disease and lung cancer mortality, for which previous studies have reported consistent and strong inverse associations with own BMI, suggests that such studies have overstated the apparent adverse consequences of lower BMI with respect to these outcomes.
Contributors: GDS developed the idea for this study. FR and PT constructed the dataset, and JACS carried out the statistical analysis. GDS led the writing of the paper, with substantial contributions from JACS, AF, PT, DAL, and FR. FR, JACS, and GDS act as guarantors for the paper.
Funding: The Medical Research Council (G0600705) and the University of Bristol provide core funding for the Medical Research Council Centre of Causal Analyses in Translational Epidemiology. JACS and DAL were also funded by Medical Research Council collaborative project grant G0601625. AF is funded by a Medical Research Council research fellowship. The views expressed in this paper are those of the authors and not necessarily those of any funding body or others whose support is acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: None declared.
Ethical approval: The study was approved by the Regional Ethical Review Board, Stockholm Sweden.
Data sharing: No additional data available.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.