Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
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 t... Mehr ...
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| Dokumenttyp: | Artikel |
| Erscheinungsdatum: | 2015 |
| Reihe/Periodikum: | Nature Communications, vol 6, iss 1 |
| Verlag/Hrsg.: |
eScholarship
University of California |
| Schlagwörter: | Genetics / Human Genome / Aetiology / 2.1 Biological and endogenous factors / Cardiovascular / ATP-Binding Cassette Transporters / Cholesterol / Gene Frequency / Genetic Association Studies / Humans / Mutation / Missense / Netherlands / Genome of The Netherlands Consortium |
| Sprache: | unknown |
| Permalink: | https://search.fid-benelux.de/Record/base-30408462 |
| Datenquelle: | BASE; Originalkatalog |
| Powered By: | BASE |
| Link(s) : | https://escholarship.org/uc/item/0pf7030w |
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.