Serum Lipids in the GENECARD Study of Coronary Artery Disease Identify Quantitative Trait Loci and Phenotypic Subsets on Chromosomes 3q and 5q

  title={Serum Lipids in the GENECARD Study of Coronary Artery Disease Identify Quantitative Trait Loci and Phenotypic Subsets on Chromosomes 3q and 5q},
  author={S. H. Shah and William E. Kraus and David C Crossman and Christopher B. Granger and Jonathan L. Haines and C J H Jones and Vincent Mooser and L Huang and Carol Haynes and Elaine Dowdy and Gloria Lena Vega and Scott M. Grundy and Jeffery M. Vance and Elizabeth R. Hauser},
  journal={Annals of Human Genetics},
Coronary artery disease (CAD) and dyslipidemia have strong genetic components. Heterogeneity complicates evaluating genetics of complex diseases such as CAD; incorporating disease‐related phenotypes may help reduce heterogeneity. We hypothesized that incorporating lipoproteins in a study of CAD would increase the power to map genes, narrow linkage peaks, identify phenotypic subsets, and elucidate the contribution of established risk factors to genetic results. 

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD are identified: EBF1, PPP2R2B, SPOCK1, and PRELID2, which should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.

Pilot Genome wide Linkage Analysis in Asian Indian Families with Coronary Artery Disease

Novel loci on chromosome 4,6 and 8 has shown suggestive evidence of linkage to CAD; their role in the etio-pathogenesis of CAD remains to be established.

Estimating the Genetic Variance of Five Lipid-Relevant Genes for Determining the Plasma Lipid Profiles

It is identified that the genetic variance for the total cholesterol, HDL-ch cholesterol and LDL-cholesterol, and the LDL-C/HDL-C ratio was significantly influenced by the genetic polymorphisms in 5 candidate genes in the Korean population.

Gene–smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort

A pathway-based analysis of the association results using WebGestalt revealed several enriched pathways including the regulation of the actin cytoskeleton pathway as defined by the Kyoto Encyclopedia of Genes and Genomes.

A treasure trove for lipoprotein biology

Three new genome-wide association studies of thousands of individuals now identify seven genes or loci contributing to lipid concentrations and confirm a number of previously reported associations.

High heritability of metabolomic profiles in families burdened with premature cardiovascular disease

A novel finding of high heritabilities of metabolites in premature CAD is reported, establishing a possible genetic basis for these profiles and implications for understanding CAD pathophysiology and genetics.

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene

Analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal–medial thickness (CCIMT), supporting a proposed model of gene- by- stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself.

Peakwide mapping on chromosome 3q13 identifies the kalirin gene as a novel candidate gene for coronary artery disease.

The data suggest the importance of the KALRN gene and the Rho GTPase-signaling pathway in the pathogenesis of CAD and the peakwide survey found evidence of association in SNPs from multiple genes.

GATA2 Is Associated with Familial Early-Onset Coronary Artery Disease

Observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary arteries disease inheritance.



Genetics of lipoprotein abnormalities associated with coronary artery disease susceptibility.

  • J. Breslow
  • Biology, Medicine
    Annual review of genetics
  • 2000
The future should provide the capability to perform reasonable genetic profiling for lipoprotein abnormalities associated with coronary heart disease susceptibility, with more and more studies combining linkage analysis with genome scans to identify new loci that influence lipop protein phenotypes.

Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome.

Pedigree-based analysis using a variance components linkage model demonstrated a quantitative trait locus (QTL) on chromosome 3 (3q27) strongly linked to six traits representing these fundamental phenotypes, and candidate genes likely to influence two biologic precursor pathways of the metabolic syndrome are identified.

Genomewide scan for familial combined hyperlipidemia genes in finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels.

Additional putative loci influencing FCHL in Finnish families, some potentially affecting TG levels and some potentially affected TC or apoB levels are suggested.

Design of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study.

Analysis of the study population revealed a strong concordance of known cardiac risk factors among affected sibling pairs, which will have implications for stratifying populations for the statistical analysis of the genome scan and on the choice of covariates for the follow-up studies of the initial genome screen analysis.

Linkage of familial combined hyperlipidaemia to chromosome 1q21–q23

The identification of a mouse combined hyperlipidaemia locus in the syntenic region of the mouse genome is reported, thus further implicating a gene in this region in the aetiology of FCHL.

A comprehensive linkage analysis for myocardial infarction and its related risk factors

It is shown, by using variance component analysis and incorporating risk factors, that risk of myocardial infarction maps to a single region on chromosome 14 with a significant lod score of 3.9, providing evidence of a principal MI locus.

A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study.

DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis and identifies a region on chromosome 3q13 that is linked to early-onset CAD.

Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1)

Familial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both, is observed in about 20% of individuals with premature coronary heart disease and is linked and associated with the gene encoding upstream transcription factor 1 (USF1) in 60 extended families with FCHL.

Genome-Wide Linkage Analysis of the Acute Coronary Syndrome Suggests a Locus on Chromosome 2

This genome scan in acute coronary syndrome suggests 1 locus that encompasses the gene encoding the insulin receptor substrate-1 gene, and two other potential loci were identified, implying that a limited number of potent susceptibility genes exist for the acute coronary Syndrome.