Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout

Abstract Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilib...

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Autores principales:	Charleen D. Adams, Brian B. Boutwell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6c6a9e3f7469421abbeac1d41ffdb7b7
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spelling	oai:doaj.org-article:6c6a9e3f7469421abbeac1d41ffdb7b72021-12-02T18:03:05ZUsing multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout10.1038/s41598-021-97410-42045-2322https://doaj.org/article/6c6a9e3f7469421abbeac1d41ffdb7b72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97410-4https://doaj.org/toc/2045-2322Abstract Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (r g ). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P-value = 1.2E−17; r g = 0.25 [P-value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P-value = 1.2E−21; r g = 0.23 [P-value = 8.8E−12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = − 0.083; 95% CI = − 0.101, − 0.065; P-value = 2.5E−19; r g = − 0.28; [P-value = 5.2E−24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P-value = 8.9E−14; r g = 0.29 [P-value = 0.001]) and higher HDL decreased urate (beta = − 0.109; 95% CI = − 0.148, − 0.071; P-value = 2.7E− 08; r g = − 0.21 [P-value = 9.8E−05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P-value = 1.1E−130; r g = 0.89 [P-value = 1.7E−55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P-value = 1.3E−04; r g = 0.23 [P-value = 2.7E−05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = −0.011; 95% CI = −0.030, 0.008; P-value = 2.6E−01; r g = 0.03 [P-value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity’s impact on urate was exacerbated by it decreasing HDL.Charleen D. AdamsBrian B. BoutwellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charleen D. Adams Brian B. Boutwell Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
description	Abstract Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (r g ). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P-value = 1.2E−17; r g = 0.25 [P-value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P-value = 1.2E−21; r g = 0.23 [P-value = 8.8E−12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = − 0.083; 95% CI = − 0.101, − 0.065; P-value = 2.5E−19; r g = − 0.28; [P-value = 5.2E−24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P-value = 8.9E−14; r g = 0.29 [P-value = 0.001]) and higher HDL decreased urate (beta = − 0.109; 95% CI = − 0.148, − 0.071; P-value = 2.7E− 08; r g = − 0.21 [P-value = 9.8E−05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P-value = 1.1E−130; r g = 0.89 [P-value = 1.7E−55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P-value = 1.3E−04; r g = 0.23 [P-value = 2.7E−05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = −0.011; 95% CI = −0.030, 0.008; P-value = 2.6E−01; r g = 0.03 [P-value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity’s impact on urate was exacerbated by it decreasing HDL.
format	article
author	Charleen D. Adams Brian B. Boutwell
author_facet	Charleen D. Adams Brian B. Boutwell
author_sort	Charleen D. Adams
title	Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
title_short	Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
title_full	Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
title_fullStr	Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
title_full_unstemmed	Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
title_sort	using multiple mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6c6a9e3f7469421abbeac1d41ffdb7b7
work_keys_str_mv	AT charleendadams usingmultiplemendelianrandomizationapproachesandgeneticcorrelationstounderstandobesityurateandgout AT brianbboutwell usingmultiplemendelianrandomizationapproachesandgeneticcorrelationstounderstandobesityurateandgout
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Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout

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