Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

Chasman, Daniel I.; Paré, Guillaume; Mora, Samia; Hopewell, Jemma C.; Peloso, Gina M.; Clarke, Robert; Cupples, L. Adrienne; Hamsten, Anders; Kathiresan, Sekar; Mälarstig, Anders; Ordovas, José M.; Ripatti, Samuli; Parker, Alex; Miletich, Joseph P.; Ridker, Paul M.

doi:10.1371/journal.pgen.1000730

Cited by 306 publications

(336 citation statements)

References 38 publications

Supporting

Mentioning

296

Contrasting

Unclassified

Order By: Relevance

“…Methodologies for quantifying HDL subpopulations (HDL 2 and HDL 3 ) and particle size (small, intermediate, and large) are only now becoming more accurate and available for larger study samples (such as NMR-based measurements). Two recent studies have examined specialized lipid phenotypes in thousands of subjects ( 123,229 ). One of these studies has investigated the signifi cant GWA loci with ApoA1, HDL 2 , HDL 3 , and HDL size among other specialized phenotypes ( 123 ).…”

Section: Family Studies In Investigation Of Private Variantsmentioning

confidence: 99%

Genetic causes of high and low serum HDL-cholesterol

Weissglas‐Volkov

Pajukanta

2010

Journal of Lipid Research

180

132

View full text Add to dashboard Cite

Section: Family Studies In Investigation Of Private Variantsmentioning

confidence: 99%

Genetic causes of high and low serum HDL-cholesterol

Weissglas‐Volkov

Pajukanta

2010

Journal of Lipid Research

180

132

View full text Add to dashboard Cite

“…We also analyzed a variant rs1367117, which has been reported to have POE on glucose level [6,42]. No significant association between the level of glucose from NMR metabolite panel and this variant was detected in our data.…”

Section: Resultsmentioning

confidence: 72%

“…In addition to the genome-wide analysis, we selected previously established associations from the study by Kettunen et al [9], where meta-analysis of 123 metabolites in 24,925 individuals revealed 62 associations with NMR metabolite levels, and tested if any of these associations show POEs. In total, five loci had p-values less than 0.05 (Supplementary Table 1), but none of them reached the threshold considered for significance after multiple testing correction (p corrected < 0.001).We also analyzed a variant rs1367117, which has been reported to have POE on glucose level [6,42]. No significant association between the level of glucose from NMR metabolite panel and this variant was detected in our data.…”

mentioning

confidence: 83%

Genome-Wide Analysis of Nuclear Magnetic Resonance Metabolites Revealed Parent-of-Origin Effect on Triglycerides in Medium Very Low-Density Lipoprotein in PTPRD Gene

et al. 2018

View full text Add to dashboard Cite

Aim:The aim of the study was to explore the parent-of-origin effects (POEs) on a range of human nuclear magnetic resonance metabolites. Materials & methods: We search for POEs in 14,815 unrelated individuals from Estonian and Finnish cohorts using POE method for the genotype data imputed with 1000 G reference panel and 82 nuclear magnetic resonance metabolites. Results: Meta-analysis revealed the evidence of POE for the variant rs1412727 in PTPRD gene for the metabolite: triglycerides in medium very low-density lipoprotein. No POEs were detected for genetic variants that were previously known to have main effect on circulating metabolites. Conclusion: We demonstrated possibility to detect POEs for human metabolites, but the POEs are weak, and therefore it is hard to detect those using currently available sample sizes. Circulating metabolites are intermediate products of metabolic processes that are known to participate in a wide spectrum of biological pathways and consequently associated with many diseases and pathological conditions [1]. In this context, metabolites could be used as a system-wide connection from genetic variants to disease-or phenotypic outcome. Therefore, identification of genetic variants associated with these molecules is an important task of genome-wide association studies (GWAS) [2][3][4][5][6]. The advances in proton nuclear magnetic resonance ( 1 H-NMR or shortened as NMR) spectroscopy provide a method for quantifying of a wide range of high and low molecular weight compounds without any prior selection [7]. To date, the NHGRI-EBI Catalog of published GWAS reports approximately 1529 genetic variants in 58 studies associated with different kind of metabolic phenotypes measured from diverse range of different tissue samples [8]. The most comprehensive GWAS of NMR metabolites to date was performed by Kettunen et al. where profiles of metabolic measures were analyzed in up to 25,000 individuals and 62 associations with various metabolites were described [9].Although GWAS have been more successful discovering genetic variants associated with human metabolites, there is still a large proportion of 'hidden heritability'. As a source of genetic variance, several analyses have been proposed, including those focusing on rare variants, structural variants, gene-gene and gene-environment interactions and parent-of-origin effects (POEs) [10,11]. POEs reflect a combination of genetic and epigenetic mechanisms, modulating different complex traits associated mainly with embryonic growth and development [12] and these effects have been described with many complex diseases such as diabetes mellitus, disglycemia and retinoblastoma [13][14][15]. In case of POEs, not only the presence of an allele, but also its parental origin affects the phenotypic outcome [16]. As an example, maternal allele-specific association of a common variant (rs1367117) located in the APOB gene was demonstrated in the analysis of adiposity [17] and borderline significant effect for fasting glucose and insulin levels [17]. This nonsy...

show abstract

“…Anyhow, the capacity of newer genetic loci of predicting future CV risk is estimated to be modest. Strong and reproducible results were reached in GWAS and other association studies related to lipid metabolism: GWAS have so far identified 43 loci involved with lipoprotein metabolism (131,132). For example, SNPs consistently associated to LDL levels were located in previously identified loci (ABCA1, APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG, and PCSK9) and new ones (CELSR2-PSRC1-SORT1) (133,134).…”

Section: Coronary Calciummentioning

confidence: 92%

From circulating biomarkers to genomics and imaging in the prediction of cardiovascular events in the general population

et al. 2011

View full text Add to dashboard Cite

From circulating biomarkers to genomics and imaging in the prediction of cardiovascular events in the general population. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Abstract Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. In the last decades numerous markers have been considered and investigated for the prediction of CV events, but only a few of them resulted in improved global risk assessment beyond traditional risk factors when incorporated into coronary evaluation scores. Recent genetic studies have pointed out a few but consistent loci or genes which are independently associated with CV risk. The idea is fascinating that these genetic markers could lead to improved individual CV risk assessment and tailored pharmacological interventions. In this brief review we will not make a systematic review of all non-genetic and genetic markers of CV risk but we will try to make a brief overview of the most interesting ones with the aim to underline potential ' pros ' and ' cons ' of their implementation in clinical practice. From circulating biomarkers to genomics and imaging in the prediction of cardiovascular events in the general population

show abstract

Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

Cited by 306 publications

References 38 publications

Genetic causes of high and low serum HDL-cholesterol

Genetic causes of high and low serum HDL-cholesterol

Genome-Wide Analysis of Nuclear Magnetic Resonance Metabolites Revealed Parent-of-Origin Effect on Triglycerides in Medium Very Low-Density Lipoprotein in PTPRD Gene

From circulating biomarkers to genomics and imaging in the prediction of cardiovascular events in the general population

Contact Info

Product

Resources

About