Estimating the genetically predicted effects of lifestyle risk factors, educational attainment and Alzheimer’s disease liability on weight change during midlife

Abstract

AbstractBackgroundWeight change is a major indicator of adverse health outcomes. This study aims to examine factors contributing to weight change over a one-year interval in midlife.MethodsObservational and one-sample Mendelian randomisation (MR) analyses were conducted to estimate effects on weight change compared to one year previously (mean age: 56.5 years) using data from the UK Biobank study (n=453,169). Risk factors included alcohol consumption, smoking intensity, body mass index (BMI), educational attainment and Alzheimer’s disease liability.ResultsObservational analyses indicated strong evidence of an association between greater educational attainment and family history of Alzheimer’s disease with weight loss. In contrast, smoking intensity and higher BMI were associated with weight gain. MR analyses were consistent with observational estimates for educational attainment and Alzheimer’s disease liability on weight loss and provided strong evidence of a genetically predicted effect between higher overall BMI and weight gain. Whilst there was little evidence of a genetically predicted effect between smoking intensity and weight change in those who had ever smoked, when stratified, smoking intensity was associated with weight loss in current smokers and weight gain in previous smokers. There was little evidence of an association between alcohol consumption and weight change in the one-year period. Inverse probability weighting was used to account for non-random selection on smoking and alcohol status and further stratification by smoking status, indicating that our results were largely robust to collider bias.ConclusionsIndividuals who have been in education for longer, may have more opportunity to reduce their weight in midlife. The effect of Alzheimer’s disease liability on weight loss could be indicative of early signs of dementia. The relationship between smoking intensity and weight change is complex, reinforcing the importance of combining interventions aimed at controlling weight and smoking cessation among cigarette smokers.Key MessagesObservational and Mendelian randomisation analyses used in this study provide consistent evidence that educational attainment and Alzheimer’s disease liability have an effect on weight loss over one year during midlife.This suggests that individuals experiencing unintentional weight loss in midlife may be at high risk of developing Alzheimer’s disease in later life.These results additionally demonstrate the value of Mendelian randomisation in minimising spurious associations obtained through observational research when assessing lifestyle risk factors prone to residual confounding, such as smoking intensity.Our findings show that the relationship between smoking and weight change is complex, endorsing the notion that strategies to tackle weight control and smoking cessation should be combined.