Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

The Genome of the Netherlands Consortium

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Article number6065
JournalNature Communications
Volume6
DOIs
StatePublished - Mar 9 2015
Externally publishedYes

Fingerprint

genome
Netherlands
cholesterol
lipids
Genes
Cholesterol
Genome
Lipids
blood
Blood
Population
phenotype
loci
genes
low frequencies
Phenotype
Testing

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels. / The Genome of the Netherlands Consortium.

In: Nature Communications, Vol. 6, 6065, 09.03.2015.

Research output: Contribution to journalArticle

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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.",
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AU - Van Leeuwen, Elisabeth M.

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AU - Deelen, Joris

AU - Isaacs, Aaron

AU - Medina-Gomez, Carolina

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AU - Francioli, Laurent C.

AU - Menelaou, Androniki

AU - Pulit, Sara L.

AU - Rivadeneira, Fernando

AU - Hofman, Albert

AU - Oostra, Ben A.

AU - Franco, Oscar H.

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AU - Rotter, Jerome I.

AU - Mychaleckyj, Josyf C.

AU - Campbell, Harry

AU - Duan, Qing

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AU - Hormozdiari, Fereydoun

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