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

KORA Study Group

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3635-3646
Number of pages12
JournalHuman Molecular Genetics
Volume25
Issue number16
DOIs
Publication statusPublished - 2015

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Genome-Wide Association Study
Meta-Analysis
Single Nucleotide Polymorphism
Kidney
Triglycerides
HDL Cholesterol
apolipoprotein A-IV
Chylomicrons
Genetic Loci
Alleles
Cholesterol
Lipids

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations. / KORA Study Group.

In: Human Molecular Genetics, Vol. 25, No. 16, 2015, p. 3635-3646.

Research output: Contribution to journalArticle

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abstract = "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.",
author = "{KORA Study Group} and Claudia Lamina and Salome Friedel and Stefan Coassin and Rico Rueedi and Noha Yousri and Ilkka Sepp{\"a}l{\"a} and Christian Gieger and Sebastian Sch{\"o}nherr and Lukas Forer and Gertraud Erhart and Barbara Kollerits and Pedro Marques-Vidal and Janina Ried and Gerard Waeber and Sven Bergmann and Doreen D{\"a}hnhardt and Andrea St{\"o}ckl and Stefan Kiechl and Raitakari, {Olli T.} and Mika K{\"a}h{\"o}nen and Johann Willeit and Ludmilla Kedenko and Bernhard Paulweber and Annette Peters and Thomas Meitinger and Konstantin Strauch and Terho Lehtim{\"a}ki and Steven Hunt and Peter Vollenweider and Florian Kronenberg",
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AU - KORA Study Group

AU - Lamina, Claudia

AU - Friedel, Salome

AU - Coassin, Stefan

AU - Rueedi, Rico

AU - Yousri, Noha

AU - Seppälä, Ilkka

AU - Gieger, Christian

AU - Schönherr, Sebastian

AU - Forer, Lukas

AU - Erhart, Gertraud

AU - Kollerits, Barbara

AU - Marques-Vidal, Pedro

AU - Ried, Janina

AU - Waeber, Gerard

AU - Bergmann, Sven

AU - Dähnhardt, Doreen

AU - Stöckl, Andrea

AU - Kiechl, Stefan

AU - Raitakari, Olli T.

AU - Kähönen, Mika

AU - Willeit, Johann

AU - Kedenko, Ludmilla

AU - Paulweber, Bernhard

AU - Peters, Annette

AU - Meitinger, Thomas

AU - Strauch, Konstantin

AU - Lehtimäki, Terho

AU - Hunt, Steven

AU - Vollenweider, Peter

AU - Kronenberg, Florian

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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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