Functional validation of new pathways in lipoprotein metabolism identified by human genetics

@article{Bauer2011FunctionalVO,
  title={Functional validation of new pathways in lipoprotein metabolism identified by human genetics},
  author={Robert C. Bauer and Ioannis M Stylianou and Daniel J. Rader},
  journal={Current Opinion in Lipidology},
  year={2011},
  volume={22},
  pages={123–128}
}
Purpose of review Recent genome-wide association studies (GWAS) have identified approximately 100 genomic loci that are associated with plasma lipid traits, two-thirds of which had never been previously associated with lipoprotein metabolism. Identification of the causal genes and variants, functional validation of these genes and biological pathways, and elucidation of molecular mechanisms is required and poses a daunting task. Recent findings Human genetics have been used to recently… 
Genetics-driven discovery of novel regulators of lipid metabolism
TLDR
Increased focus on the translation rather than the discovery of these loci, with new attention paid to lncRNAs, can help spur the development of novel therapeutics targeting lipid metabolism.
Integrated approaches to functionally characterize novel factors in lipoprotein metabolism
  • H. Runz
  • Biology, Medicine
    Current opinion in lipidology
  • 2012
TLDR
If and how the combined analysis of large-scale datasets from multiple independent sources benefits the mapping of novel genetic elements with relevance to lipoprotein metabolism and allows for conclusions on underlying molecular mechanisms is discussed.
Finding genes and variants for lipid levels after genome-wide association analysis
TLDR
The main findings from genome-wide association studies for levels of HDL-cholesterol, LDL-ch cholesterol and triglycerides are reviewed, including approaches to identify the functional variant or gene, and study design and challenges related to whole genome or exome sequencing to identify novel genes and variants are discussed.
The tribbles gene family and lipoprotein metabolism.
TLDR
This review attempts to synthesize knowledge obtained on the biology of the tribbles protein family in the context of lipid metabolism as well as discussing the recently emerging genetic evidence for the importance of these proteins in human disease.
Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease
TLDR
Findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.
Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol
TLDR
The findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci.
Allelic and phenotypic spectrum of plasma triglycerides.
Emerging LDL therapies: Using human genetics to discover new therapeutic targets for plasma lipids.
Tribbles-1: a novel regulator of hepatic lipid metabolism in humans
TLDR
Tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target, including developing TRIB1-based lipid therapeutics.
...
1
2
3
4
...

References

SHOWING 1-10 OF 39 REFERENCES
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population
TLDR
The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.
Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids
TLDR
The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus
TLDR
Functional evidence for a novel regulatory pathway for lipoprotein metabolism is provided and it is suggested that modulation of this pathway may alter risk for MI in humans.
Trib1 is a lipid- and myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice.
TLDR
Functional evidence is provided for what is believed to be a novel gene regulating hepatic lipogenesis and VLDL production in mice that influences plasma lipids and risk for myocardial infarction in humans.
Newly identified loci that influence lipid concentrations and risk of coronary artery disease
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising
Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
TLDR
The first GWA analysis of loci affecting total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform establishes 22 loci associated with serum lipid levels at genome-wide significance level.
Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans.
TLDR
ANGPTL3, Angiopoietin-like proteins, but not ANGPTL6, play nonredundant roles in TG metabolism, and multiple alleles at these loci cumulatively contribute to variability in plasma TG levels in humans.
Genomewide association analysis of coronary artery disease.
TLDR
Several genetic loci that, individually and in aggregate, substantially affect the risk of development of coronary artery disease are identified.
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
TLDR
Using genome-wide association data from three studies and targeted replication association analyses in up to 18,554 independent participants, it is shown that common SNPs at 18 loci are reproducibly associated with concentrations of low-density cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides.
...
1
2
3
4
...