Instrumental variable analysis using offspring BMI in childhood as an indicator of parental BMI in relation to mortality

Kim Blond,Thorkild I A Sørensen,George Davey Smith,Dorte Vistisen,Jennifer L Baker,David Carslake,Line Klingen Gjærde

doi:10.1038/s41598-021-01352-w

Abstract

Childhood BMI shows associations with adult mortality, but these may be influenced by effects of ill health in childhood on BMI and later mortality. To avoid this, we used offspring childhood BMI as an instrumental variable (IV) for own BMI in relation to mortality and compared it with conventional associations of own childhood BMI and own mortality. We included 36,097 parent–offspring pairs with measured heights and weights from the Copenhagen School Health Records Register and register-based information on death. Hazard ratios (HR) were estimated using adjusted Cox regression models. For all-cause mortality, per zBMI at age 7 the conventional HR = 1.07 (95%CI: 1.04–1.09) in women and 1.02 (95%CI: 0.92–1.14) in men, whereas the IV HR = 1.23 (95%CI: 1.15–1.32) in women and 1.05 (95%CI: 0.94–1.17) in men. Per zBMI at age 13, the conventional HR = 1.11 (95%CI: 1.08–1.15) in women and 1.03 (95%CI: 0.99–1.06) in men, whereas the IV HR = 1.30 (95%CI: 1.19–1.42) in women and 1.15 (95%CI: 1.04–1.29) in men. Only conventional models showed indications of J-shaped associations. Our IV analyses suggest that there is a causal relationship between BMI and mortality that is positive at both high and low BMI values.

Highlights

Children, and especially adolescents, with obesity have a higher mortality rate than children with normal weight[1,2,3,4,5]
Among 36,097 parent–offspring pairs, we found positive associations at age 7 and 13 for all-cause mortality, CVD mortality and cancer mortality
For all-cause mortality and CVD mortality, we found stronger Hazard ratios (HR) per zBMI in instrumental variable (IV) models than in conventional models

Summary

Introduction

Especially adolescents, with obesity have a higher mortality rate than children with normal weight[1,2,3,4,5]. There are indications that low body mass index (BMI) values in childhood are associated with increased adult m ortality[6,7] in a manner similar to associations between adulthood BMI and m ortality[8] These associations may be influenced by disease and general ill health that affect child BMI and adult mortality[9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]. The intergenerational association in BMI is caused by heritability of a mixture of exposures which differ by age as, for example, alcohol consumption and tobacco have minimal roles in child BMI, but constitute a part of the heritability of adult B MI30,31 As such offspring childhood BMI as the IV likely represents a somewhat different exposure than offspring adulthood BMI does. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Scientific Reports | (2021) 11:22408

Methods

Results

Conclusion