Jun 12, 2014

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

European Journal of Human Genetics : EJHG
Jorie VersmissenE J G Sijbrands

Abstract

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17,000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10(-4)). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance a...Continue Reading

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  • Citations6

References

Mentioned in this Paper

LDLR wt Allele
Genome-Wide Association Study
LDLR
Hypercholesterolemia, Familial
Odds Ratio
Coronary Arteriosclerosis
Hyperlipoproteinemia Type IIa
Nested Case-Control Studies
Genetic Equilibrium
Comorbidity

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