Evidence for the genetic influence of waist-hip ratio on risk of kidney stone disease
BAUS ePoster online library. Lovegrove C. 06/21/21; 319104; p6-6
Disclosure(s): NIHR Academic Clinical Fellow
Ms. Catherine Lovegrove
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Abstract
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Introduction
Kidney stone disease (KSD) is a common condition with a poorly understood pathogenesis. Stones are associated with hypertension, cardiovascular disease, and diabetes, all of which have been linked to central adiposity. To increase understanding of the pathophysiological mechanisms underlying this condition we explored the relationship of waist:hip ratio (WHR), as a marker of central adiposity, with risk of KSD using conventional and genetic epidemiological analyses.
Patients and methods:
Data from 492,380 UK Biobank participants were examined for associations of WHR with incident KSD using multivariate Cox-proportional hazard models. To explore causal relationships between higher WHR and KSD, Mendelian randomisation (MR) was undertaken using 380 genetic variants associated with increased WHR as instrumental variables.
Results:
After adjustment for age, sex, activity, deprivation, smoking status and diet, WHR was significantly associated with risk of incident nephrolithiasis. In overweight patients, high WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation. MR demonstrated that one standard deviation increase in genetically instrumented WHR was associated with 43% increased risk of KSD (OR 1.43, 95% CI 1.25-1.64, P=3.57x10^-7, Figure 1). This causal relationship persisted in sensitivity analyses, including adjustment for BMI.
Conclusion:
Central adiposity is associated with increased risk of kidney stone formation. Our genetic analyses indicate that central adiposity is an important cause of kidney stones. These findings motivate weight management as an adjunctive therapeutic approach in the treatment and prevention of nephrolithiasis and will facilitate future work investigating the mechanisms whereby central adiposity cause an increased risk of stone formation.
Kidney stone disease (KSD) is a common condition with a poorly understood pathogenesis. Stones are associated with hypertension, cardiovascular disease, and diabetes, all of which have been linked to central adiposity. To increase understanding of the pathophysiological mechanisms underlying this condition we explored the relationship of waist:hip ratio (WHR), as a marker of central adiposity, with risk of KSD using conventional and genetic epidemiological analyses.
Patients and methods:
Data from 492,380 UK Biobank participants were examined for associations of WHR with incident KSD using multivariate Cox-proportional hazard models. To explore causal relationships between higher WHR and KSD, Mendelian randomisation (MR) was undertaken using 380 genetic variants associated with increased WHR as instrumental variables.
Results:
After adjustment for age, sex, activity, deprivation, smoking status and diet, WHR was significantly associated with risk of incident nephrolithiasis. In overweight patients, high WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation. MR demonstrated that one standard deviation increase in genetically instrumented WHR was associated with 43% increased risk of KSD (OR 1.43, 95% CI 1.25-1.64, P=3.57x10^-7, Figure 1). This causal relationship persisted in sensitivity analyses, including adjustment for BMI.
Conclusion:
Central adiposity is associated with increased risk of kidney stone formation. Our genetic analyses indicate that central adiposity is an important cause of kidney stones. These findings motivate weight management as an adjunctive therapeutic approach in the treatment and prevention of nephrolithiasis and will facilitate future work investigating the mechanisms whereby central adiposity cause an increased risk of stone formation.
Introduction
Kidney stone disease (KSD) is a common condition with a poorly understood pathogenesis. Stones are associated with hypertension, cardiovascular disease, and diabetes, all of which have been linked to central adiposity. To increase understanding of the pathophysiological mechanisms underlying this condition we explored the relationship of waist:hip ratio (WHR), as a marker of central adiposity, with risk of KSD using conventional and genetic epidemiological analyses.
Patients and methods:
Data from 492,380 UK Biobank participants were examined for associations of WHR with incident KSD using multivariate Cox-proportional hazard models. To explore causal relationships between higher WHR and KSD, Mendelian randomisation (MR) was undertaken using 380 genetic variants associated with increased WHR as instrumental variables.
Results:
After adjustment for age, sex, activity, deprivation, smoking status and diet, WHR was significantly associated with risk of incident nephrolithiasis. In overweight patients, high WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation. MR demonstrated that one standard deviation increase in genetically instrumented WHR was associated with 43% increased risk of KSD (OR 1.43, 95% CI 1.25-1.64, P=3.57x10^-7, Figure 1). This causal relationship persisted in sensitivity analyses, including adjustment for BMI.
Conclusion:
Central adiposity is associated with increased risk of kidney stone formation. Our genetic analyses indicate that central adiposity is an important cause of kidney stones. These findings motivate weight management as an adjunctive therapeutic approach in the treatment and prevention of nephrolithiasis and will facilitate future work investigating the mechanisms whereby central adiposity cause an increased risk of stone formation.
Kidney stone disease (KSD) is a common condition with a poorly understood pathogenesis. Stones are associated with hypertension, cardiovascular disease, and diabetes, all of which have been linked to central adiposity. To increase understanding of the pathophysiological mechanisms underlying this condition we explored the relationship of waist:hip ratio (WHR), as a marker of central adiposity, with risk of KSD using conventional and genetic epidemiological analyses.
Patients and methods:
Data from 492,380 UK Biobank participants were examined for associations of WHR with incident KSD using multivariate Cox-proportional hazard models. To explore causal relationships between higher WHR and KSD, Mendelian randomisation (MR) was undertaken using 380 genetic variants associated with increased WHR as instrumental variables.
Results:
After adjustment for age, sex, activity, deprivation, smoking status and diet, WHR was significantly associated with risk of incident nephrolithiasis. In overweight patients, high WHR (men >0.9, women >0.85) conferred >40% increased risk of stone formation. MR demonstrated that one standard deviation increase in genetically instrumented WHR was associated with 43% increased risk of KSD (OR 1.43, 95% CI 1.25-1.64, P=3.57x10^-7, Figure 1). This causal relationship persisted in sensitivity analyses, including adjustment for BMI.
Conclusion:
Central adiposity is associated with increased risk of kidney stone formation. Our genetic analyses indicate that central adiposity is an important cause of kidney stones. These findings motivate weight management as an adjunctive therapeutic approach in the treatment and prevention of nephrolithiasis and will facilitate future work investigating the mechanisms whereby central adiposity cause an increased risk of stone formation.
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