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

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  • 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
  • And 105 others
  • 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
  • Ozren Polasek
  • Veronique Vitart
  • Igor Rudan
  • Alan F. Wright
  • Stephen S. Rich
  • Bruce M. Psaty
  • Ingrid B. Borecki
  • Patricia M. Kearney
  • David J. Stott
  • L. Adrienne Cupples
  • J. Wouter Jukema
  • Pim Van Der Harst
  • Eric J. Sijbrands
  • Jouke Jan Hottenga
  • Andre G. Uitterlinden
  • Morris A. Swertz
  • Gert Jan B Van Ommen
  • Paul I W De Bakker
  • P. Eline Slagboom
  • Dorret I. Boomsma
  • Cisca Wijmenga
  • Cornelia M. Van Duijn
  • Pieter B T Neerincx
  • Clara C. Elbers
  • Pier Francesco Palamara
  • Itsik Peer
  • Abdel Abdellaoui
  • Wigard P. Kloosterman
  • Mannis Van Oven
  • Martijn Vermaat
  • Mingkun Li
  • Jeroen F J Laros
  • Mark Stoneking
  • Peter De Knijff
  • Manfred Kayser
  • Jan H. Veldink
  • Leonard H. Van Den Berg
  • Heorhiy Byelas
  • Johan T. Den Dunnen
  • Martijn Dijkstra
  • Najaf Amin
  • K. Joeri Van Der Velde
  • Jessica Van Setten
  • Mathijs Kattenberg
  • Barbera D C Van Schaik
  • Jan Bot
  • Isaäc J. Nijman
  • Hailiang Mei
  • Vyacheslav Koval
  • Kai Ye
  • Eric Wubbo Lameijer
  • Matthijs H. Moed
  • Jayne Y. Hehir-Kwa
  • Robert E. Handsaker
  • Shamil R. Sunyaev
  • Mashaal Sohail
  • Fereydoun Hormozdiari
  • Tobias Marschall
  • Alexander Schönhuth
  • Victor Guryev
  • H. Eka D Suchiman
  • Bruce H. Wolffenbuttel
  • Mathieu Platteel
  • Steven J. Pitts
  • Shobha Potluri
  • David R. Cox
  • Qibin Li
  • Yingrui Li
  • Yuanping Du
  • Ruoyan Chen
  • Hongzhi Cao
  • Ning Li
  • Sujie Cao
  • Jun Wang
  • Jasper A. Bovenberg

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 -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
Article number6065
JournalNature Communications
Volume6
Number of pages6
ISSN2041-1723
DOIs
Publication statusPublished - 2015

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