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

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State: Public
Version: Final published version
Serval ID
serval:BIB_323B694F448A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.
Journal
Human molecular genetics
Author(s)
Lamina C., Friedel S., Coassin S., Rueedi R., Yousri N.A., Seppälä I., Gieger C., Schönherr S., Forer L., Erhart G., Kollerits B., Marques-Vidal P., Ried J., Waeber G., Bergmann S., Dähnhardt D., Stöckl A., Kiechl S., Raitakari O.T., Kähönen M., Willeit J., Kedenko L., Paulweber B., Peters A., Meitinger T., Strauch K., Study Group K., Lehtimäki T., Hunt S.C., Vollenweider P., Kronenberg F.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
15/08/2016
Peer-reviewed
Oui
Volume
25
Number
16
Pages
3635-3646
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.

Pubmed
Open Access
Yes
Create date
03/10/2016 11:10
Last modification date
20/08/2019 13:17
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