Biological, clinical and population relevance of 95 loci for blood lipids

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Detaljer

Författare
  • Tanya M. Teslovich
  • Kiran Musunuru
  • Albert V. Smith
  • Andrew C. Edmondson
  • Ioannis M. Stylianou
  • Masahiro Koseki
  • James P. Pirruccello
  • Samuli Ripatti
  • Daniel I. Chasman
  • Cristen J. Willer
  • Christopher T. Johansen
  • Sigrid W. Fouchier
  • Aaron Isaacs
  • Gina M. Peloso
  • Maja Barbalic
  • Sally L. Ricketts
  • Joshua C. Bis
  • Yurii S. Aulchenko
  • Gudmar Thorleifsson
  • Mary F. Feitosa
  • John Chambers
  • Toby Johnson
  • Xiaohui Li
  • Xiuqing Guo
  • Mingyao Li
  • Yoon Shin Cho
  • Min Jin Go
  • Young Jin Kim
  • Jong-Young Lee
  • Taesung Park
  • Kyunga Kim
  • Xueling Sim
  • Rick Twee-Hee Ong
  • Damien C. Croteau-Chonka
  • Leslie A. Lange
  • Joshua D. Smith
  • Kijoung Song
  • Jing Hua Zhao
  • Xin Yuan
  • Jian'an Luan
  • Claudia Lamina
  • Andreas Ziegler
  • Weihua Zhang
  • Robert Y. L. Zee
  • Alan F. Wright
  • Jacqueline C. M. Witteman
  • James F. Wilson
  • Gonneke Willemsen
  • H. -Erich Wichmann
  • John B. Whitfield
  • Dawn M. Waterworth
  • Nicholas J. Wareham
  • Gerard Waeber
  • Peter Vollenweider
  • Benjamin F. Voight
  • Veronique Vitart
  • Andre G. Uitterlinden
  • Manuela Uda
  • Jaakko Tuomilehto
  • John R. Thompson
  • Toshiko Tanaka
  • Ida Surakka
  • Heather M. Stringham
  • Tim D. Spector
  • Nicole Soranzo
  • Johannes H. Smit
  • Juha Sinisalo
  • Kaisa Silander
  • Eric J. G. Sijbrands
  • Angelo Scuteri
  • James Scott
  • David Schlessinger
  • Serena Sanna
  • Veikko Salomaa
  • Juha Saharinen
  • Chiara Sabatti
  • Aimo Ruokonen
  • Igor Rudan
  • Lynda M. Rose
  • Robert Roberts
  • Mark Rieder
  • Bruce M. Psaty
  • Peter P. Pramstaller
  • Irene Pichler
  • Markus Perola
  • Brenda W. J. H. Penninx
  • Nancy L. Pedersen
  • Cristian Pattaro
  • Alex N. Parker
  • Guillaume Pare
  • Ben A. Oostra
  • Christopher J. O'Donnell
  • Markku S. Nieminen
  • Deborah A. Nickerson
  • Grant W. Montgomery
  • Thomas Meitinger
  • Ruth McPherson
  • Mark I. McCarthy
  • Wendy McArdle
  • David Masson
  • Nicholas G. Martin
  • Fabio Marroni
  • Massimo Mangino
  • Patrik K. E. Magnusson
  • Gavin Lucas
  • Robert Luben
  • Ruth J. F. Loos
  • Marja-Liisa Lokki
  • Guillaume Lettre
  • Claudia Langenberg
  • Lenore J. Launer
  • Edward G. Lakatta
  • Reijo Laaksonen
  • Kirsten O. Kyvik
  • Florian Kronenberg
  • Inke R. Koenig
  • Kay-Tee Khaw
  • Jaakko Kaprio
  • Lee M. Kaplan
  • Asa Johansson
  • Marjo-Riitta Jarvelin
  • A. Cecile J. W. Janssens
  • Erik Ingelsson
  • Wilmar Igi
  • G. Kees Hovingh
  • Jouke-Jan Hottenga
  • Albert Hofman
  • Andrew A. Hicks
  • Christian Hengstenberg
  • Iris M. Heid
  • Caroline Hayward
  • Aki S. Havulinna
  • Nicholas D. Hastie
  • Tamara B. Harris
  • Talin Haritunians
  • Alistair S. Hall
  • Ulf Gyllensten
  • Candace Guiducci
  • Elena Gonzalez
  • Christian Gieger
  • Nelson B. Freimer
  • Luigi Ferrucci
  • Jeanette Erdmann
  • Paul Elliott
  • Kenechi G. Ejebe
  • Angela Doering
  • Anna F. Dominiczak
  • Serkalem Demissie
  • Panagiotis Deloukas
  • Eco J. C. de Geus
  • Ulf de Faire
  • Gabriel Crawford
  • Francis S. Collins
  • Yii-der I. Chen
  • Mark J. Caulfield
  • Harry Campbell
  • Noel P. Burtt
  • Lori L. Bonnycastle
  • Dorret I. Boomsma
  • S. Matthijs Boekholdt
  • Richard N. Bergman
  • Ines Barroso
  • Stefania Bandinelli
  • Christie M. Ballantyne
  • Themistocles L. Assimes
  • Thomas Quertermous
  • David Altshuler
  • Mark Seielstad
  • Tien Y. Wong
  • E-Shyong Tai
  • Alan B. Feranil
  • Christopher W. Kuzawa
  • Linda S. Adair
  • Herman A., Jr. Taylor
  • Ingrid B. Borecki
  • Stacey B. Gabriel
  • James G. Wilson
  • Hilma Holm
  • Unnur Thorsteinsdottir
  • Vilmundur Gudnason
  • Ronald M. Krauss
  • Karen L. Mohlke
  • Jose M. Ordovas
  • Patricia B. Munroe
  • Jaspal S. Kooner
  • Alan R. Tall
  • Robert A. Hegele
  • John J. P. Kastelein
  • Eric E. Schadt
  • Jerome I. Rotter
  • Eric Boerwinkle
  • David P. Strachan
  • Vincent Mooser
  • Kari Stefansson
  • Muredach P. Reilly
  • Nilesh J. Samani
  • Heribert Schunkert
  • L. Adrienne Cupples
  • Manjinder S. Sandhu
  • Paul M. Ridker
  • Daniel J. Rader
  • Cornelia M. van Duijn
  • Leena Peltonen
  • Goncalo R. Abecasis
  • Michael Boehnke
  • Sekar Kathiresan
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
  • Kardiologi
Originalspråkengelska
Sidor (från-till)707-713
TidskriftNature
Volym466
Utgivningsnummer7307
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa