Forskning ved Københavns Universitet - Københavns Universitet

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Exome-wide association study of plasma lipids in >300,000 individuals

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  • Dajiang J. Liu
  • Gina M. Peloso
  • Haojie Yu
  • Adam S. Butterworth
  • Xiao Wang
  • Anubha Mahajan
  • Danish Saleheen
  • Connor Emdin
  • Dewan Alam
  • Alexessander Couto Alves
  • Philippe Amouyel
  • Emanuele DI Angelantonio
  • Dominique Arveiler
  • Themistocles L. Assimes
  • Paul L. Auer
  • Usman Baber
  • Christie M. Ballantyne
  • Lia E. Bang
  • Joshua C. Bis
  • Michael Boehnke
  • Eric Boerwinkle
  • Jette Bork-Jensen
  • Erwin P. Bottinger
  • Ivan Brandslund
  • Morris Brown
  • Fabio Busonero
  • Mark J. Caulfield
  • John C. Chambers
  • Daniel I. Chasman
  • Y. Eugene Chen
  • Yii Der Ida Chen
  • Rajiv Chowdhury
  • Cramer Christensen
  • Audrey Y. Chu
  • John M. Connell
  • Francesco Cucca
  • L. Adrienne Cupples
  • Scott M. Damrauer
  • Gail Davies
  • Ian J. Deary
  • George Dedoussis
  • Joshua C. Denny
  • Anna Dominiczak
  • Marie Pierre Dubé
  • Tapani Ebeling
  • Gudny Eiriksdottir
  • Toñu Esko
  • Aliki Eleni Farmaki
  • Mary F. Feitosa
  • Marco Ferrario
  • Jean Ferrieres
  • Ian Ford
  • Myriam Fornage
  • Paul W. Franks
  • Timothy M. Frayling
  • Lars G. Fritsche
  • Philippe Frossard
  • Valentin Fuster
  • Santhi K. Ganesh
  • Wei Gao
  • Melissa E. Garcia
  • Christian Gieger
  • Franco Giulianini
  • Mark O. Goodarzi
  • Harald Grallert
  • Leif Groop
  • Megan L. Grove
  • Vilmundur Gudnason
  • Tamara B. Harris
  • Caroline Hayward
  • Joel N. Hirschhorn
  • Oddgeir L. Holmen
  • Jennifer Huffman
  • Yong Huo
  • Kristian Hveem
  • Sehrish Jabeen
  • Anne U. Jackson
  • Johanna Jakobsdottir
  • Marjo Riitta Jarvelin
  • Gorm B. Jensen
  • Marit E. Jørgensen
  • J. Wouter Jukema
  • Pia R. Kamstrup
  • Stavroula Kanoni
  • Fredrik Karpe
  • Frank Kee
  • Amit V. Khera
  • Derek Klarin
  • Heikki A. Koistinen
  • Jaspal S. Kooner
  • Charles Kooperberg
  • Kari Kuulasmaa
  • Johanna Kuusisto
  • Markku Laakso
  • Timo Lakka
  • Claudia Langenberg
  • Anne Langsted
  • Lenore J. Launer
  • Torsten Lauritzen
  • David C. MLiewald
  • Li An Lin
  • Ruth J.F. Loos
  • Yingchang Lu
  • Xiangfeng Lu
  • Reedik Mägi
  • Anders Malarstig
  • Ani Manichaikul
  • Alisa K. Manning
  • Pekka Mäntyselkä
  • Eirini Marouli
  • Nicholas G.D. Masca
  • Andrea Maschio
  • James B. Meigs
  • Olle Melander
  • Andres Metspalu
  • Andrew P. Morris
  • Alanna C. Morrison
  • Antonella Mulas
  • Martina Müller-Nurasyid
  • Patricia B. Munroe
  • Matt J. Neville
  • Sune F. Nielsen
  • Jonas B. Nielsen
  • Jose M. Ordovas
  • Roxana Mehran
  • Christoper J. O'Donnell
  • Marju Orho-Melander
  • Cliona M. Molony
  • Pieter Muntendam
  • Sandosh Padmanabhan
  • Colin N.A. Palmer
  • Dorota Pasko
  • Aniruddh P. Patel
  • Markus Perola
  • Annette Peters
  • Giorgio Pistis
  • Ozren Polasek
  • Neil Poulter
  • Bruce M. Psaty
  • Daniel J. Rader
  • Asif Rasheed
  • Rainer Rauramaa
  • Dermot F. Reilly
  • Alex P. Reiner
  • Frida Renström
  • Stephen S. Rich
  • Paul M. Ridker
  • John D. Rioux
  • Neil R. Robertson
  • Dan M. Roden
  • Jerome I. Rotter
  • Igor Rudan
  • Veikko Salomaa
  • Nilesh J. Samani
  • Serena Sanna
  • Naveed Sattar
  • Ellen M. Schmidt
  • Robert A. Scott
  • Peter Sever
  • Raquel S. Sevilla
  • Christian M. Shaffer
  • Xueling Sim
  • Suthesh Sivapalaratnam
  • Kerrin S. Small
  • Albert V. Smith
  • Blair H. Smith
  • Sangeetha Somayajula
  • Lorraine Southam
  • Timothy D. Spector
  • Elizabeth K. Speliotes
  • John M. Starr
  • Kathleen E. Stirrups
  • Nathan Stitziel
  • Konstantin Strauch
  • Heather M. Stringham
  • Praveen Surendran
  • Hayato Tada
  • Alan R. Tall
  • Hua Tang
  • Jean Claude Tardif
  • Kent D. Taylor
  • Stella Trompet
  • Philip S. Tsao
  • Jaakko Tuomilehto
  • Natalie R.Van Zuydam
  • Anette Varbo
  • Tibor V. Varga
  • Jarmo Virtamo
  • Melanie Waldenberger
  • Nan Wang
  • Nick J. Wareham
  • Helen R. Warren
  • Peter E. Weeke
  • Joshua Weinstock
  • Jennifer Wessel
  • James G. Wilson
  • Peter W.F. Wilson
  • Ming Xu
  • Hanieh Yaghootkar
  • Robin Young
  • Eleftheria Zeggini
  • He Zhang
  • Neil S. Zheng
  • Weihua Zhang
  • Yan Zhang
  • Wei Zhou
  • Yanhua Zhou
  • Magdalena Zoledziewska
  • Joanna M.M. Howson
  • John Danesh
  • Mark I. McCarthy
  • Chad A. Cowan
  • Goncalo Abecasis
  • Panos Deloukas
  • Kiran Musunuru
  • Cristen J. Willer
  • Sekar Kathiresan

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind49
Udgave nummer12
Sider (fra-til)1758-1766
Antal sider9
ISSN1061-4036
DOI
StatusUdgivet - 1 dec. 2017

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