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A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms
High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association stu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580897/ https://www.ncbi.nlm.nih.gov/pubmed/28512139 http://dx.doi.org/10.1194/jlr.M076232 |
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author | Mack, Salome Coassin, Stefan Rueedi, Rico Yousri, Noha A. Seppälä, Ilkka Gieger, Christian Schönherr, Sebastian Forer, Lukas Erhart, Gertraud Marques-Vidal, Pedro Ried, Janina S. Waeber, Gerard Bergmann, Sven Dähnhardt, Doreen Stöckl, Andrea Raitakari, Olli T. Kähönen, Mika Peters, Annette Meitinger, Thomas Strauch, Konstantin Kedenko, Ludmilla Paulweber, Bernhard Lehtimäki, Terho Hunt, Steven C. Vollenweider, Peter Lamina, Claudia Kronenberg, Florian |
author_facet | Mack, Salome Coassin, Stefan Rueedi, Rico Yousri, Noha A. Seppälä, Ilkka Gieger, Christian Schönherr, Sebastian Forer, Lukas Erhart, Gertraud Marques-Vidal, Pedro Ried, Janina S. Waeber, Gerard Bergmann, Sven Dähnhardt, Doreen Stöckl, Andrea Raitakari, Olli T. Kähönen, Mika Peters, Annette Meitinger, Thomas Strauch, Konstantin Kedenko, Ludmilla Paulweber, Bernhard Lehtimäki, Terho Hunt, Steven C. Vollenweider, Peter Lamina, Claudia Kronenberg, Florian |
author_sort | Mack, Salome |
collection | PubMed |
description | High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 × 10(−30)). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to be significantly associated with Lp(a) concentrations (P = 3.47 × 10(−10)). Each APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population’s mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the TLR2 gene with Lp(a) (P = 3.4 × 10(−4)). In summary, we identified a large number of independent SNPs in the LPA gene region, as well as the APOE2 allele, to be significantly associated with Lp(a) concentrations. |
format | Online Article Text |
id | pubmed-5580897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-55808972017-11-03 A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms Mack, Salome Coassin, Stefan Rueedi, Rico Yousri, Noha A. Seppälä, Ilkka Gieger, Christian Schönherr, Sebastian Forer, Lukas Erhart, Gertraud Marques-Vidal, Pedro Ried, Janina S. Waeber, Gerard Bergmann, Sven Dähnhardt, Doreen Stöckl, Andrea Raitakari, Olli T. Kähönen, Mika Peters, Annette Meitinger, Thomas Strauch, Konstantin Kedenko, Ludmilla Paulweber, Bernhard Lehtimäki, Terho Hunt, Steven C. Vollenweider, Peter Lamina, Claudia Kronenberg, Florian J Lipid Res Research Articles High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio = 1.73, P = 3.35 × 10(−30)). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the APOE2-determining allele of rs7412 to be significantly associated with Lp(a) concentrations (P = 3.47 × 10(−10)). Each APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the population’s mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the TLR2 gene with Lp(a) (P = 3.4 × 10(−4)). In summary, we identified a large number of independent SNPs in the LPA gene region, as well as the APOE2 allele, to be significantly associated with Lp(a) concentrations. The American Society for Biochemistry and Molecular Biology 2017-09 2017-05-16 /pmc/articles/PMC5580897/ /pubmed/28512139 http://dx.doi.org/10.1194/jlr.M076232 Text en Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/4.0/ Author’s Choice—Final version free via Creative Commons CC-BY license. |
spellingShingle | Research Articles Mack, Salome Coassin, Stefan Rueedi, Rico Yousri, Noha A. Seppälä, Ilkka Gieger, Christian Schönherr, Sebastian Forer, Lukas Erhart, Gertraud Marques-Vidal, Pedro Ried, Janina S. Waeber, Gerard Bergmann, Sven Dähnhardt, Doreen Stöckl, Andrea Raitakari, Olli T. Kähönen, Mika Peters, Annette Meitinger, Thomas Strauch, Konstantin Kedenko, Ludmilla Paulweber, Bernhard Lehtimäki, Terho Hunt, Steven C. Vollenweider, Peter Lamina, Claudia Kronenberg, Florian A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title | A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title_full | A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title_fullStr | A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title_full_unstemmed | A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title_short | A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
title_sort | genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580897/ https://www.ncbi.nlm.nih.gov/pubmed/28512139 http://dx.doi.org/10.1194/jlr.M076232 |
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