Educational Inequality in Multimorbidity: Causality and Causal Pathways. A Mendelian Randomisation Study in UK Biobank
Authors: North Teri-Louise , Harrison Sean , Bishop Deborah C , Wootton Robyn , Carter Alice R , Richardson Tom G , Payne Rupert A , Salisbury Chris , Howe Laura D 
Published: June 2022

ABSTRACTObjectivesMultimorbidity, typically defined as having two or more long-term health conditions, is a common patient characteristic that is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity may help with the design and prioritisation of interventions to prevent multimorbidity. This study examined potential causal determinants (education, BMI, smoking and alcohol consumption) of multimorbidity, and assessed the extent to which BMI, smoking and alcohol consumption explain observed educational inequalities in multimorbidity.DesignMendelian randomization study; an approach that uses genetic variants as instrumental variables to interrogate causality.Participants181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank.Main outcome measuresMultimorbidity status (2+ self-reported health conditions); secondary analyses considered complex multimorbidity defined as 3+ or 4+ conditions, and a continuous multimorbidity score.ResultsMendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in BMI is associated with a 9.2% increased risk of multimorbidity (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index is associated with a 6.8% increased risk of multimorbidity (95% CI: 3.3 to 10.4%). Evidence for a causal effect of alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity (2+ conditions) by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity.ConclusionsEducation, BMI, smoking and alcohol consumption are intervenable risk factors that our results suggest have a causal effect on multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.SUMMARY BOXSECTION 1: WHAT IS ALREADY KNOWN ON THIS TOPIC-Multimorbidity has several known lifestyle and anthropometric risk factors and is associated with deprivation.-The effect of education (proxying deprivation) on multimorbidity is likely mediated by some of these intervenable risk factors.-These associations are likely to be confounded and their causality is not well understood.SECTION 2: WHAT THIS STUDY ADDS-Analyses using genetically predicted effects suggest that education, BMI, smoking and alcohol consumption each have a causal effect on multimorbidity and that 32% of the educational inequality in multimorbidity is attributable to BMI and smoking combined.