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.

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Contributor The Genome of the Netherlands Consortium
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Journal Nature Communications
van Leeuwen, E.M, Karssen, L.C, Deelen, J, Isaacs, A, Medina-Gomez, M.C, Mbarek, H, … van Duijn, C.M. (2015). Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels. Nature Communications, 6. doi:10.1038/ncomms7065