Do Serum Urate–Associated Genetic Variants Differentially Contribute to Gout Risk According to Body Mass Index? Analysis of the UK Biobank

2020 ◽  
Vol 72 (7) ◽  
pp. 1184-1191 ◽  
Author(s):  
Vicky Tai ◽  
Ravi K. Narang ◽  
Greg Gamble ◽  
Murray Cadzow ◽  
Lisa K. Stamp ◽  
...  
2020 ◽  
Vol 105 (12) ◽  
pp. e4688-e4698
Author(s):  
Zhi Cao ◽  
Chenjie Xu ◽  
Hongxi Yang ◽  
Shu Li ◽  
Fusheng Xu ◽  
...  

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Ravi K. Narang ◽  
Ruth Topless ◽  
Murray Cadzow ◽  
Greg Gamble ◽  
Lisa K. Stamp ◽  
...  

2017 ◽  
Vol 2 (8) ◽  
pp. 882 ◽  
Author(s):  
Donald M. Lyall ◽  
Carlos Celis-Morales ◽  
Joey Ward ◽  
Stamatina Iliodromiti ◽  
Jana J. Anderson ◽  
...  

PLoS Medicine ◽  
2019 ◽  
Vol 16 (12) ◽  
pp. e1002982 ◽  
Author(s):  
Michael Wainberg ◽  
Anubha Mahajan ◽  
Anshul Kundaje ◽  
Mark I. McCarthy ◽  
Erik Ingelsson ◽  
...  

2020 ◽  
Vol 47 (11) ◽  
pp. 1704-1711
Author(s):  
Ravi K. Narang ◽  
Greg Gamble ◽  
Amanda J. Phipps-Green ◽  
Ruth Topless ◽  
Murray Cadzow ◽  
...  

ObjectiveThe aim of this study was to determine whether serum urate (SU)–associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic.MethodsThis research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use. Gene-diuretic interactions for gout association were tested using a genetic risk score (GRS) and individual SNP by logistic regression adjusting for relevant confounders.ResultsAfter adjustment, use of a loop diuretic was positively associated with prevalent gout (OR 2.34, 95% CI 2.08–2.63), but thiazide diuretics were inversely associated with prevalent gout (OR 0.60, 95% CI 0.55–0.66). Compared with a lower GRS (< mean), a higher GRS (≥ mean) was positively associated with gout in those not taking diuretics (OR 2.63, 2.49–2.79), in those taking loop diuretics (OR 2.04, 95% CI 1.65–2.53), in those taking thiazide diuretics (OR 2.70, 2.26–3.23), and in those taking thiazide-like diuretics (OR 2.11, 95% CI 1.37–3.25). No nonadditive gene-diuretic interactions were observed.ConclusionIn people taking diuretics, SU-associated genetic variants contribute strongly to gout risk, with a similar effect to that observed in those not taking a diuretic. These findings suggest that the contribution of genetic variants is not restricted to people with “primary” gout, and that genetic variants can play an important role in gout susceptibility in the presence of other risk factors.


2020 ◽  
Author(s):  
Jujiao Kang ◽  
Tianye Jia ◽  
Zeyu Jiao ◽  
Chun Shen ◽  
Chao Xie ◽  
...  

AbstractObjectiveTo explore how different diets may affect human brain development and if genetic and environmental factors play a part.DesignCohort study.SettingUK Biobank data were collected from 22 centres across the UK.ParticipantsOnly white British individuals free of Alzheimer’s or dementia diseases were included in the study, where 336517 participants had quality-controlled genetic data, and 18879 participants had qualified brain MRI data.Main outcome measuresGrey matter volume, intake of cereal and coffee, body mass index and blood cholesterol level.ResultsWe investigated diet effects in the UK Biobank data and discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. These genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions.ConclusionsOur findings revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.


Author(s):  
Ling-Li Zeng ◽  
Christopher R. K. Ching ◽  
Zvart Abaryan ◽  
Sophia I. Thomopoulos ◽  
Kai Gao ◽  
...  

2021 ◽  
Author(s):  
Jeremy A Labrecque ◽  
Sonja A Swanson

Estimates from conventional Mendelian randomization (MR) analyses can be biased when the genetic variants proposed as instruments vary over age in their relationship with the exposure. For four exposures commonly studied using MR, we assessed the degree to which their relationship with genetic variants commonly used as instruments varies by age using flexible, spline-based models in UK Biobank data. Using these models, we then estimated how biased MR estimates would be due to age-varying relationships using plasmode simulations. We found that most genetic variants had age-varying relationships with the exposure for which they are a proposed instrument. Body mass index and LDL cholesterol had the most variation while alcohol consumption had very little. This variation over age led to small potential biases in some cases (e.g. alcohol consumption and C-reactive protein) and large potential biases for many proposed instruments for BMI and LDL.


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