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Applying genome-wide approach to define the genetics of low-density lipoprotein oxidation in two large cohorts

MÄKELÄ, KARI-MATTI (2013)

 
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MÄKELÄ, KARI-MATTI
2013

Bioinformatiikka - Bioinformatics
Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology
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Hyväksymispäivämäärä
2013-02-18
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https://urn.fi/urn:nbn:fi:uta-1-23232
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Background: Cardiovascular diseases (CVD) are the number one killer and cause of disability in today’s world. Oxidized low-density lipoprotein (oxLDL) is considered to be a key factor in the development of atherosclerosis which leads to CVD. The genetics of LDL oxidation are poorly known.

Aims: In this work, I continued and extended our previously published genome-wide association study (GWAS) on oxLDL. Previously, single-nucleotide polymorphisms (SNP) were imputed to HapMap2 reference with 2.2 million variants. The aim of the present study was to find novel SNPs associated with oxLDL in a meta-analysis of two GWASs with SNPs imputed now to the 1000 genomes reference (ca. 20 million variants).

Materials and Methods: GWASs were performed on a population of young healthy individuals (A: N=2,080, 45% male, aged 32±5 years, with the SNPTEST software), and in a patient sample (B: N=2,912, 69% male, 63±11 years, with the ProbABEL software), and a combined GWAS meta-analysis for cohort A and B data was carried out using the GWAMA software. Furthermore, the GWAS was run in the A population with top-SNP adjustment.

Results: The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B (apoB) was the only SNP independently associated with oxLDL (p=8.7 x 10-168) in the GWAS meta-analysis. This is in accordance with our previously published study, and no new genome-wide significant hits were found.  

Conclusions: No new oxLDL levels related SNPs were found in this study. The next step is to study the specific effects of rs676210 and its environmental factor interactions with cardiovascular endpoints more closely.
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Kalevantie 5
PL 617
33014 Tampereen yliopisto
oa[@]tuni.fi | Tietosuoja | Saavutettavuusseloste