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A genome-wide association meta-analysis on apolipoprotein A-IV concentrations

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known...

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Autores principales: Lamina, Claudia, Friedel, Salome, Coassin, Stefan, Rueedi, Rico, Yousri, Noha A., Seppälä, Ilkka, Gieger, Christian, Schönherr, Sebastian, Forer, Lukas, Erhart, Gertraud, Kollerits, Barbara, Marques-Vidal, Pedro, Ried, Janina, Waeber, Gerard, Bergmann, Sven, Dähnhardt, Doreen, Stöckl, Andrea, Kiechl, Stefan, Raitakari, Olli T., Kähönen, Mika, Willeit, Johann, Kedenko, Ludmilla, Paulweber, Bernhard, Peters, Annette, Meitinger, Thomas, Strauch, Konstantin, Study Group, KORA, Lehtimäki, Terho, Hunt, Steven C., Vollenweider, Peter, Kronenberg, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179953/
https://www.ncbi.nlm.nih.gov/pubmed/27412012
http://dx.doi.org/10.1093/hmg/ddw211
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author Lamina, Claudia
Friedel, Salome
Coassin, Stefan
Rueedi, Rico
Yousri, Noha A.
Seppälä, Ilkka
Gieger, Christian
Schönherr, Sebastian
Forer, Lukas
Erhart, Gertraud
Kollerits, Barbara
Marques-Vidal, Pedro
Ried, Janina
Waeber, Gerard
Bergmann, Sven
Dähnhardt, Doreen
Stöckl, Andrea
Kiechl, Stefan
Raitakari, Olli T.
Kähönen, Mika
Willeit, Johann
Kedenko, Ludmilla
Paulweber, Bernhard
Peters, Annette
Meitinger, Thomas
Strauch, Konstantin
Study Group, KORA
Lehtimäki, Terho
Hunt, Steven C.
Vollenweider, Peter
Kronenberg, Florian
author_facet Lamina, Claudia
Friedel, Salome
Coassin, Stefan
Rueedi, Rico
Yousri, Noha A.
Seppälä, Ilkka
Gieger, Christian
Schönherr, Sebastian
Forer, Lukas
Erhart, Gertraud
Kollerits, Barbara
Marques-Vidal, Pedro
Ried, Janina
Waeber, Gerard
Bergmann, Sven
Dähnhardt, Doreen
Stöckl, Andrea
Kiechl, Stefan
Raitakari, Olli T.
Kähönen, Mika
Willeit, Johann
Kedenko, Ludmilla
Paulweber, Bernhard
Peters, Annette
Meitinger, Thomas
Strauch, Konstantin
Study Group, KORA
Lehtimäki, Terho
Hunt, Steven C.
Vollenweider, Peter
Kronenberg, Florian
author_sort Lamina, Claudia
collection PubMed
description Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (−) (44)), rs5104 in APOA4 (P = 1.79 × 10(−)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(−)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (−) (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(−)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1. The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.
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spelling pubmed-51799532016-12-27 A genome-wide association meta-analysis on apolipoprotein A-IV concentrations Lamina, Claudia Friedel, Salome Coassin, Stefan Rueedi, Rico Yousri, Noha A. Seppälä, Ilkka Gieger, Christian Schönherr, Sebastian Forer, Lukas Erhart, Gertraud Kollerits, Barbara Marques-Vidal, Pedro Ried, Janina Waeber, Gerard Bergmann, Sven Dähnhardt, Doreen Stöckl, Andrea Kiechl, Stefan Raitakari, Olli T. Kähönen, Mika Willeit, Johann Kedenko, Ludmilla Paulweber, Bernhard Peters, Annette Meitinger, Thomas Strauch, Konstantin Study Group, KORA Lehtimäki, Terho Hunt, Steven C. Vollenweider, Peter Kronenberg, Florian Hum Mol Genet Association Studies Articles Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 (−) (44)), rs5104 in APOA4 (P = 1.79 × 10(−)(24)) and rs4241819 in KLKB1 (P = 5.6 × 10(−)(14)). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 (−) (07)). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10(−)(05)). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1. The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations. Oxford University Press 2016-08-15 2016-07-12 /pmc/articles/PMC5179953/ /pubmed/27412012 http://dx.doi.org/10.1093/hmg/ddw211 Text en © The Author 2016. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Association Studies Articles
Lamina, Claudia
Friedel, Salome
Coassin, Stefan
Rueedi, Rico
Yousri, Noha A.
Seppälä, Ilkka
Gieger, Christian
Schönherr, Sebastian
Forer, Lukas
Erhart, Gertraud
Kollerits, Barbara
Marques-Vidal, Pedro
Ried, Janina
Waeber, Gerard
Bergmann, Sven
Dähnhardt, Doreen
Stöckl, Andrea
Kiechl, Stefan
Raitakari, Olli T.
Kähönen, Mika
Willeit, Johann
Kedenko, Ludmilla
Paulweber, Bernhard
Peters, Annette
Meitinger, Thomas
Strauch, Konstantin
Study Group, KORA
Lehtimäki, Terho
Hunt, Steven C.
Vollenweider, Peter
Kronenberg, Florian
A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title_full A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title_fullStr A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title_full_unstemmed A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title_short A genome-wide association meta-analysis on apolipoprotein A-IV concentrations
title_sort genome-wide association meta-analysis on apolipoprotein a-iv concentrations
topic Association Studies Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179953/
https://www.ncbi.nlm.nih.gov/pubmed/27412012
http://dx.doi.org/10.1093/hmg/ddw211
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