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

Article scientifique 2017 Anglais

Résumé

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).

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Mack, S., Coassin, S., Vaucher, J., Kronenberg, F., Lamina, C., Rueedi, R., Yousri, N., Seppälä, I., Gieger, C., Schönherr, S., Forer, L., Erhart, G., Kollerits, B., Marques‐Vidal, P., Müller‐Nurasyid, M., Waeber, G., Bergmann, S., Dähnhardt, D., Stöckl, A., Kiechl, S., Raitakari, O., Kähönen, M., Willeit, J., Kedenko, L., Paulweber, B., Peters, A., Meitinger, T., Strauch, K., Lehtimäki, T., Hunt, S., Vollenweider, P. (2017). Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study. https://doi.org/10.1038/s41598-017-07213-9

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Auteur(s)

Salome Rebecca Mack Stefan Coassin Julien Vaucher Florian Kronenberg Claudia Lamina Rico Rueedi Noha A. Yousri Ilkka Seppälä Christian Gieger Sebastian Schönherr Lukas Forer Gertraud Erhart Barbara Kollerits Pedro Marques‐Vidal Martina Müller‐Nurasyid Gérard Waeber Sven Bergmann Doreen Dähnhardt Andrea Stöckl Stefan Kiechl Olli T. Raitakari Mika Kähönen Johann Willeit Ludmilla Kedenko Bernhard Paulweber Annette Peters Thomas Meitinger Konstantin Strauch Terho Lehtimäki Steven C. Hunt Péter Vollenweider

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