Abstract

BackgroundMendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES).MethodsUK Biobank data for 482,127 subjects was linked with HES inpatient admission records, and costs were assigned to episodes of care. A two-stage least squares (TSLS) IV model and a TSLS two-part cost model were compared to a naïve regression of inpatient healthcare costs on body mass index (BMI).ResultsThe naïve analysis of annual cost on continuous BMI predicted an annual cost of £21.61 [95% CI £20.33 – £22.89] greater cost per unit increase in BMI. The TSLS IV model predicted an annual cost of £14.36 [95% CI £0.31 – £28.42] greater cost per unit increase in BMI. Modelled with a binary obesity variable, the naïve analysis predicted that obese subjects incurred £205.53 [95% CI £191.45 – £219.60] greater costs than non-obese subjects. The TSLS model predicted a cost £201.58 [95% CI £4.32 – £398.84] greater for obese subjects compared to non-obese subjects.ConclusionsThe IV models provide evidence for a causal relationship between obesity and higher inpatient healthcare costs. Compared to the naïve models, the binary IV model found a slightly smaller marginal effect of obesity, and the continuous IV model found a slightly smaller marginal effect of a single unit increase in BMI.

Highlights

  • Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors

  • Our study aims to use Mendelian Randomization (MR) to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES)

  • The instrument was significantly associated with ethnicity (p < 0.001), which suggests a possible violation of the independence assumption by population stratification, which occurs when alleles occur with different frequencies in a population subgroup [22]

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Summary

Introduction

Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES). The global prevalence of obesity has increased significantly since 1980 and represents a significant economic burden worldwide [1,2,3,4,5]. Analysis of Global Burden of Disease data (2015) estimated that 603.7 million adults were obese, representing 12% of adults globally [6]. Obesity has a significant impact on health through secondary consequences such as type 2 diabetes, coronary heart disease, cancer, stroke, and depression [8,9,10]. Observational studies have established a positive correlation between elevated BMI and healthcare costs, but they cannot definitively establish causation because of the high likelihood of unobserved confounding factors

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