Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 25751400.
- Also identified by DOI 10.1038/ncomms7065 and PMC identifier 4366498.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.
Medical subject headings
- ATP-Binding Cassette Transporters
- Cholesterol
- Mutation, Missense