A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans
Timpson, N. J., Walter, K., Min, J. L.,… & Soranzo, N., 2014.
Nature Communications, 5:4871
In this high-profile research collaboration reported in Nature Communications last month, KASP genotyping was used to validate a genotyping-by-sequencing screen of genetic variation across a population which identified a rare variant (rs138326449-A minor allele frequency ~0.25% (UK) of the APOC3 locus that is associated with lowered levels of circulating triglyceride.
Highlights of the paper
Example of a rare, large effect variant identified at a population scale.
Functional validation and analysis of the rare SNP variant effect.
KASP genotyping and validation of a minor allele frequency SNP with 100% accuracy and concordance with genotypes from the whole-genome data set.
Large study sample – KASP produced 100% accuracy over 10,145 cohort samples including 38 carriers of the rare allele.
Elevated blood lipid levels are one of the major genetic factors predisposing a person to coronary artery disease. Currently, 40-60% of the variability in lipid levels is attributed to unknown heritable genetic factors. Although genome-wide studies have investigated and identified common variants that contribute to lipid levels, these only account for 10-12% of that heritability. Whole-genome sequencing projects conducted on well-phenotyped populations offer a genuine move forward for identifying variants that may account for the unexplained heritability.
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