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

The Genome of the Netherlands Consortium

doi:10.1038/ncomms7065

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

The Genome of the Netherlands Consortium

Department of Epidemiology
Erasmus University Rotterdam
Molecular Epidemiology
Leiden University
Departments of Epidemiology Internal Medicine
Department of Biological Psychology
University of Amsterdam
Department of Genetics
University of Groningen
Department of Cardiology
Department of Gerontology and Geriatrics
Department of Cardiology
Netherlands Bioinformatics Center
BioAssist
University of Edinburgh
Department of Biostatistics
Boston University
Department of Genetics
Washington University St. Louis
Department of Biostatistics and Medicine
University of Washington
Center for Public Health Genomics
University of Virginia
Centre for Population Health Sciences
Center for Human Genetics Research
Massachusetts General Hospital
Department of Psychiatry
VU University Medical Center
Department of Medical Genetics
Utrecht University
Department of Clinical Genetics
Department of Genetical Statistics
Division of Applied Health Sciences
University of Aberdeen
Centre for Genomc and Experimental Medicine
University of Glasgow
Institute of Cardiovascular and Medical Sciences
University of Glasgow
Department of Pharmacology and Therapeutics
University College Cork
Department of Medicine
Center for Translational Genomics and Population Sciences
University of California at Los Angeles
University of North Carolina at Chapel Hill

Research output: Contribution to journal › Article › peer-review

39 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 (β_LDL-C =0.135, β_TC =0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.

Original language	English
Article number	6065
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7065
Publication status	Published - 9 Mar 2015
Externally published	Yes

Access to Document

10.1038/ncomms7065

Cite this

@article{2fbee9e43e5d4b0a8223c043deb34b70,

title = "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 {\texttimes} 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.",

author = "\{The Genome of the Netherlands Consortium\} and \{Van Leeuwen\}, \{Elisabeth M.\} and Karssen, \{Lennart C.\} and Joris Deelen and Aaron Isaacs and Carolina Medina-Gomez and Hamdi Mbarek and Alexandros Kanterakis and Stella Trompet and Iris Postmus and Niek Verweij and \{Van Enckevort\}, \{David J.\} and Huffman, \{Jennifer E.\} and White, \{Charles C.\} and Feitosa, \{Mary F.\} and Bartz, \{Traci M.\} and Ani Manichaikul and Joshi, \{Peter K.\} and Peloso, \{Gina M.\} and Patrick Deelen and \{Van Dijk\}, Freerk and Gonneke Willemsen and \{De Geus\}, \{Eco J.\} and Yuri Milaneschi and Penninx, \{Brenda W.J.H.\} and Francioli, \{Laurent C.\} and Androniki Menelaou and Pulit, \{Sara L.\} and Fernando Rivadeneira and Albert Hofman and Oostra, \{Ben A.\} and Franco, \{Oscar H.\} and Leach, \{Irene Mateo\} and Marian Beekman and \{De Craen\}, \{Anton J.M.\} and Uh, \{Hae Won\} and Holly Trochet and Hocking, \{Lynne J.\} and Porteous, \{David J.\} and Naveed Sattar and Packard, \{Chris J.\} and Buckley, \{Brendan M.\} and Brody, \{Jennifer A.\} and Bis, \{Joshua C.\} and Rotter, \{Jerome I.\} and Mychaleckyj, \{Josyf C.\} and Harry Campbell and Qing Duan and Lange, \{Leslie A.\} and Wilson, \{James F.\} and Hottenga, \{Jouke Jan\}",

year = "2015",

month = mar,

day = "9",

doi = "10.1038/ncomms7065",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

AU - The Genome of the Netherlands Consortium

AU - Van Leeuwen, Elisabeth M.

AU - Karssen, Lennart C.

AU - Deelen, Joris

AU - Isaacs, Aaron

AU - Medina-Gomez, Carolina

AU - Mbarek, Hamdi

AU - Kanterakis, Alexandros

AU - Trompet, Stella

AU - Postmus, Iris

AU - Verweij, Niek

AU - Van Enckevort, David J.

AU - Huffman, Jennifer E.

AU - White, Charles C.

AU - Feitosa, Mary F.

AU - Bartz, Traci M.

AU - Manichaikul, Ani

AU - Joshi, Peter K.

AU - Peloso, Gina M.

AU - Deelen, Patrick

AU - Van Dijk, Freerk

AU - Willemsen, Gonneke

AU - De Geus, Eco J.

AU - Milaneschi, Yuri

AU - Penninx, Brenda W.J.H.

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.

AU - Leach, Irene Mateo

AU - Beekman, Marian

AU - De Craen, Anton J.M.

AU - Uh, Hae Won

AU - Trochet, Holly

AU - Hocking, Lynne J.

AU - Porteous, David J.

AU - Sattar, Naveed

AU - Packard, Chris J.

AU - Buckley, Brendan M.

AU - Brody, Jennifer A.

AU - Bis, Joshua C.

AU - Rotter, Jerome I.

AU - Mychaleckyj, Josyf C.

AU - Campbell, Harry

AU - Duan, Qing

AU - Lange, Leslie A.

AU - Wilson, James F.

AU - Hottenga, Jouke Jan

PY - 2015/3/9

Y1 - 2015/3/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84924363528

U2 - 10.1038/ncomms7065

DO - 10.1038/ncomms7065

M3 - Article

C2 - 25751400

AN - SCOPUS:84924363528

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6065

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this