Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study

Abstract Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly avai...

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Autores principales:	Salome Mack, Stefan Coassin, Julien Vaucher, Florian Kronenberg, Claudia Lamina, ApoA-IV-GWAS Consortium
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6bac2c480c244d092f7996d10ba6b8d
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spelling	oai:doaj.org-article:d6bac2c480c244d092f7996d10ba6b8d2021-12-02T12:30:33ZEvaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study10.1038/s41598-017-07213-92045-2322https://doaj.org/article/d6bac2c480c244d092f7996d10ba6b8d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07213-9https://doaj.org/toc/2045-2322Abstract Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n = 13,813), kidney function (estimated glomerular filtration rate (eGFR), n = 133,413), lipid traits (HDL cholesterol, LDL cholesterol, triglycerides, n = 188,577), adiposity-related traits (body-mass-index (n = 322,206), waist-hip-ratio (n = 210,088)) and fasting glucose (n = 133,010). Main analyses consisted in inverse-variance weighted and multivariable MR, whereas MR-Egger regression and weighted median estimation were used as sensitivity analyses. We found that eGFR is likely to be causal on apoA-IV concentrations (53 SNPs; causal effect estimate per 1-SD increase in eGFR = −0.39; 95% CI = [−0.54, −0.24]; p-value = 2.4e-07). Triglyceride concentrations were also causally associated with apoA-IV concentrations (40 SNPs; causal effect estimate per 1-SD increase in triglycerides = −0.06; 95% CI = [−0.08, −0.04]; p-value = 4.8e-07), independently of HDL-C and LDL-C concentrations (causal effect estimate from multivariable MR = −0.06; 95% CI = [−0.10, −0.02]; p-value = 0.0014). Evaluating the inverse direction of causality revealed a possible causal association of apoA-IV on HDL-cholesterol (2 SNPs; causal effect estimate per one percent increase in apoA-IV = −0.40; 95% CI = [−0.60, −0.21]; p-value = 5.5e-05).Salome MackStefan CoassinJulien VaucherFlorian KronenbergClaudia LaminaApoA-IV-GWAS ConsortiumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Salome Mack Stefan Coassin Julien Vaucher Florian Kronenberg Claudia Lamina ApoA-IV-GWAS Consortium Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
description	Abstract Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n = 13,813), kidney function (estimated glomerular filtration rate (eGFR), n = 133,413), lipid traits (HDL cholesterol, LDL cholesterol, triglycerides, n = 188,577), adiposity-related traits (body-mass-index (n = 322,206), waist-hip-ratio (n = 210,088)) and fasting glucose (n = 133,010). Main analyses consisted in inverse-variance weighted and multivariable MR, whereas MR-Egger regression and weighted median estimation were used as sensitivity analyses. We found that eGFR is likely to be causal on apoA-IV concentrations (53 SNPs; causal effect estimate per 1-SD increase in eGFR = −0.39; 95% CI = [−0.54, −0.24]; p-value = 2.4e-07). Triglyceride concentrations were also causally associated with apoA-IV concentrations (40 SNPs; causal effect estimate per 1-SD increase in triglycerides = −0.06; 95% CI = [−0.08, −0.04]; p-value = 4.8e-07), independently of HDL-C and LDL-C concentrations (causal effect estimate from multivariable MR = −0.06; 95% CI = [−0.10, −0.02]; p-value = 0.0014). Evaluating the inverse direction of causality revealed a possible causal association of apoA-IV on HDL-cholesterol (2 SNPs; causal effect estimate per one percent increase in apoA-IV = −0.40; 95% CI = [−0.60, −0.21]; p-value = 5.5e-05).
format	article
author	Salome Mack Stefan Coassin Julien Vaucher Florian Kronenberg Claudia Lamina ApoA-IV-GWAS Consortium
author_facet	Salome Mack Stefan Coassin Julien Vaucher Florian Kronenberg Claudia Lamina ApoA-IV-GWAS Consortium
author_sort	Salome Mack
title	Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
title_short	Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
title_full	Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
title_fullStr	Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
title_full_unstemmed	Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study
title_sort	evaluating the causal relation of apoa-iv with disease-related traits - a bidirectional two-sample mendelian randomization study
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d6bac2c480c244d092f7996d10ba6b8d
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Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study

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