PMID- 27412012

OWN - NLM
STAT- MEDLINE
DCOM- 20170713
LR - 20220129
IS - 1460-2083 (Electronic)
IS - 0964-6906 (Print)
IS - 0964-6906 (Linking)
VI - 25
IP - 16
DP - 2016 Aug 15
TI - A genome-wide association meta-analysis on apolipoprotein A-IV
concentrations.
PG - 3635-3646
LID - 10.1093/hmg/ddw211 [doi]
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.
CI - © The Author 2016. Published by Oxford University Press.
FAU - Lamina, Claudia
AU - Lamina C
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Friedel, Salome
AU - Friedel S
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Coassin, Stefan
AU - Coassin S
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Rueedi, Rico
AU - Rueedi R
AD - Department of Computational Biology, University of Lausanne, Lausanne,
Switzerland.
AD - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Yousri, Noha A
AU - Yousri NA
AD - Department of Physiology and Biophysics, Weill Cornell Medical College -
Qatar,
Doha, Qatar.
AD - Department of Computer and Systems Engineering, Alexandria University,
Alexandria, Egypt.
FAU - Seppälä, Ilkka
AU - Seppälä I
AD - Department of Clinical Chemistry, Fimlab Laboratories and University of
Tampere
School of Medicine, Tampere, Finland.
FAU - Gieger, Christian
AU - Gieger C
AD - Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research
Center for Environmental Health.
AD - Institute of Epidemiology II, Helmholtz Zentrum München-German Research
Center
for Environmental Health.
AD - Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German
Research Center for Environmental Health, Neuherberg, Germany.
FAU - Schönherr, Sebastian
AU - Schönherr S
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Forer, Lukas
AU - Forer L
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Erhart, Gertraud
AU - Erhart G
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Kollerits, Barbara
AU - Kollerits B
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Marques-Vidal, Pedro
AU - Marques-Vidal P
AD - Department of Medicine, Internal Medicine, Centre Hospitalier Universitaire
Vaudois (CHUV), Lausanne, Switzerland.
FAU - Ried, Janina
AU - Ried J
AD - Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research
Center for Environmental Health.
FAU - Waeber, Gerard
AU - Waeber G
AD - Department of Medicine, Internal Medicine, Centre Hospitalier Universitaire
Vaudois (CHUV), Lausanne, Switzerland.
FAU - Bergmann, Sven
AU - Bergmann S
AD - Department of Computational Biology, University of Lausanne, Lausanne,
Switzerland.
AD - Swiss Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Dähnhardt, Doreen
AU - Dähnhardt D
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Stöckl, Andrea
AU - Stöckl A
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Kiechl, Stefan
AU - Kiechl S
AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Raitakari, Olli T
AU - Raitakari OT
AD - Department of Clinical Physiology, Turku University Hospital, Turku, Finland.
AD - Research Centre of Applied and Preventive Cardiovascular Medicine, University
of
Turku, Turku, Finland.
FAU - Kähönen, Mika
AU - Kähönen M
AD - Department of Clinical Physiology, Tampere University Hospital and University
of
Tampere, Tampere, Finland.
FAU - Willeit, Johann
AU - Willeit J
AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
FAU - Kedenko, Ludmilla
AU - Kedenko L
AD - First Department of Internal Medicine, Paracelsus Private Medical University,
Salzburg, Austria.
FAU - Paulweber, Bernhard
AU - Paulweber B
AD - First Department of Internal Medicine, Paracelsus Private Medical University,
Salzburg, Austria.
FAU - Peters, Annette
AU - Peters A
AD - Institute of Epidemiology II, Helmholtz Zentrum München-German Research
Center
for Environmental Health.
AD - DZHK (German Centre for Cardiovascular Research), partner site Munich Heart
Alliance, Munich, Germany.
AD - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
FAU - Meitinger, Thomas
AU - Meitinger T
AD - Institute of Human Genetics, Technische Universität München, München,
Germany.
AD - Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
AD - Munich Cluster for Systems Neurology (SyNergy).
FAU - Strauch, Konstantin
AU - Strauch K
AD - Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research
Center for Environmental Health.
AD - Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic
Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
CN - KORA Study Group
FAU - Lehtimäki, Terho
AU - Lehtimäki T
AD - Department of Clinical Chemistry, Fimlab Laboratories and University of
Tampere
School of Medicine, Tampere, Finland.
FAU - Hunt, Steven C
AU - Hunt SC
AD - Cardiovascular Genetics Division, University of Utah School of Medicine, Salt
Lake City, UT, USA.
AD - Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar.
FAU - Vollenweider, Peter
AU - Vollenweider P
AD - Department of Medicine, Internal Medicine, Centre Hospitalier Universitaire
Vaudois (CHUV), Lausanne, Switzerland.
FAU - Kronenberg, Florian
AU - Kronenberg F
AD - Division of Genetic Epidemiology, Department of Medical Genetics, Molecular
and
Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
LA - eng
GR - U01 HL067897/HL/NHLBI NIH HHS/United States
GR - U01 HL067896/HL/NHLBI NIH HHS/United States
GR - U01 HL067901/HL/NHLBI NIH HHS/United States
GR - U01 HL067900/HL/NHLBI NIH HHS/United States
GR - U01 HL067898/HL/NHLBI NIH HHS/United States
GR - U01 HL067894/HL/NHLBI NIH HHS/United States
GR - U01 HL067895/HL/NHLBI NIH HHS/United States
GR - U01 HL067899/HL/NHLBI NIH HHS/United States
GR - P 26660/FWF_/Austrian Science Fund FWF/Austria
GR - U01 HL067902/HL/NHLBI NIH HHS/United States
PT - Journal Article
PT - Meta-Analysis
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
DEP - 20160712
TA - Hum Mol Genet
JT - Human molecular genetics
JID - 9208958
RN - 0 (Apolipoproteins A)
RN - 0 (Cholesterol, HDL)
RN - 0 (Lipids)
RN - 0 (Triglycerides)
RN - 0 (apolipoprotein A-IV)
SB - IM
MH - Alleles
MH - Apolipoproteins A/blood/*genetics
MH - Cholesterol, HDL/blood/genetics
MH - Female
MH - *Genome-Wide Association Study
MH - Humans
MH - Kidney/metabolism
MH - Lipids/blood/genetics
MH - Male
MH - Polymorphism, Single Nucleotide/*genetics
MH - Triglycerides/blood/genetics
PMC - PMC5179953
EDAT- 2016/07/15 06:00
MHDA- 2017/07/14 06:00
CRDT- 2016/07/15 06:00
PHST- 2016/05/04 00:00 [received]
PHST- 2016/06/20 00:00 [revised]
PHST- 2016/06/27 00:00 [accepted]
PHST- 2016/07/15 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/07/15 06:00 [entrez]
AID - ddw211 [pii]
AID - 10.1093/hmg/ddw211 [doi]
PST - ppublish
SO - Hum Mol Genet. 2016 Aug 15;25(16):3635-3646. doi: 10.1093/hmg/ddw211. Epub
2016
Jul 12.