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

被引:0
作者
Elisabeth M. van Leeuwen
Lennart C. Karssen
Joris Deelen
Aaron Isaacs
Carolina Medina-Gomez
Hamdi Mbarek
Alexandros Kanterakis
Stella Trompet
Iris Postmus
Niek Verweij
David J. van Enckevort
Jennifer E. Huffman
Charles C. White
Mary F. Feitosa
Traci M. Bartz
Ani Manichaikul
Peter K. Joshi
Gina M. Peloso
Patrick Deelen
Freerk van Dijk
Gonneke Willemsen
Eco J. de Geus
Yuri Milaneschi
Brenda W.J.H. Penninx
Laurent C. Francioli
Androniki Menelaou
Sara L. Pulit
Fernando Rivadeneira
Albert Hofman
Ben A. Oostra
Oscar H. Franco
Irene Mateo Leach
Marian Beekman
Anton J.M. de Craen
Hae-Won Uh
Holly Trochet
Lynne J. Hocking
David J. Porteous
Naveed Sattar
Chris J. Packard
Brendan M. Buckley
Jennifer A. Brody
Joshua C. Bis
Jerome I. Rotter
Josyf C. Mychaleckyj
Harry Campbell
Qing Duan
Leslie A. Lange
James F. Wilson
Caroline Hayward
机构
[1] Erasmus Medical Center,Department of Epidemiology
[2] Leiden University Medical Center,Department of Molecular Epidemiology
[3] Erasmus Medical Center,Department of Epidemiology and Internal Medicine
[4] VU University Amsterdam and EMGO+ Institute for Health and Care Research,Department of Biological Psychology
[5] Genomics Coordination Center,Department of Genetics
[6] University of Groningen,Department of Cardiology
[7] University Medical Center Groningen,Department of Gerontology and Geriatrics
[8] Leiden University Medical Center,Department of Cardiology
[9] Leiden University Medical Center,Department of Biostatistics
[10] University Medical Center Groningen,Department of Genetics
[11] University of Groningen,Department of Biostatistics and Medicine
[12] BioAssist,Department of Public Health Sciences
[13] Netherlands Bioinformatics Center,Department of Psychiatry
[14] MRC Human Genetics Unit,Department of Medical Genetics
[15] MRC IGMM,Department of Clinical Genetics
[16] University of Edinburgh,Department of Genetical Statistics
[17] Boston U School of Public Health,Division of Applied Health Sciences
[18] Washington University School of Medicine,Department of Pharmacology and Therapeutics
[19] University of Washington,Department of Medicine
[20] Center for Public Health Genomics,Department of Genetics
[21] University of Virginia,Department of Public Health
[22] Centre for Population Health Sciences,Department of Medicine and Epidemiology
[23] University of Edinburgh,Department of Genetics and Biostatistics
[24] Center for Human Genetic Research,Department of Internal Medicine
[25] Massachusetts General Hospital,Department of Human Genetics
[26] VU University Medical Center Amsterdam/GGZinGeest,Department of Epidemiology
[27] EMGO+ Institute for Health and Care Research,Department of Biological Psychology
[28] Neuroscience Campus Amsterdam,Department of Genetics
[29] Center for Molecular Medicine,Department of Computer Science
[30] University Medical Center Utrecht,Department of Systems Biology
[31] Erasmus Medical Center,Department of Forensic Molecular Biology
[32] Leiden University Medical Center,Department of Human Genetics
[33] University of Aberdeen,Department of Evolutionary Genetics
[34] Centre for Genomic and Experimental Medicine,Department of Human Genetics
[35] MRC IGMM,Department of Neurology
[36] University of Edinburgh,Department of Clinical Epidemiology
[37] BHF Glasgow Cardiovascular Research Centre,Department of Human Genetics
[38] Faculty of Medicine,Department of Genetics
[39] University of Glasgow,Division of Genetics
[40] Institute of Cardiovascular and Medical Sciences,Department of Genome Sciences
[41] University of Glasgow,Department of Endocrinology
[42] University College Cork,Department of Biology
[43] University of Washington,undefined
[44] Institute for Translational Genomics and Population Sciences,undefined
[45] Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center,undefined
[46] University of North Carolina,undefined
[47] Faculty of Medicine,undefined
[48] University of Split,undefined
[49] University of Washington,undefined
[50] Washington University School of Medicine,undefined
来源
Nature Communications | / 6卷
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摘要
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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