Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
- PMID: 25751400
- PMCID: PMC4366498
- DOI: 10.1038/ncomms7065
Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
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.
Conflict of interest statement
B.M.P. served on the DSMB of a clinical trial funded by the manufacturer (Zoll Lifecor) and on the Yale Open Data Access Project funded by Johnson & Johnson. The remaining authors declare no competing financial interests.
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References
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- Genome of the Netherlands Consortium. Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nat. Genet. 46, 818–825 (2014). - PubMed
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