Discovery and refinement of loci associated with lipid levels.

Authors:
Dr. Rebecca N Nsubuga, PhD
Dr. Rebecca N Nsubuga, PhD
MRC/UVRI Uganda Research Unit on AIDS
Senior Scientist
Statistical Modelling
Entebbe | Uganda
Dr. Dharambir K Sanghera
Dr. Dharambir K Sanghera
University of Oklahoma Health Sciences Center
Professor
Oklahoma City, Oklahoma | United States
Cristen J Willer Ellen M Schmidt Sebanti Sengupta Gina M Peloso Stefan Gustafsson Stavroula Kanoni Andrea Ganna Jin Chen Martin L Buchkovich Samia Mora Jacques S Beckmann Jennifer L Bragg-Gresham Hsing-Yi Chang Ayşe Demirkan Heleen M Den Hertog Ron Do Louise A Donnelly Georg B Ehret Tõnu Esko Mary F Feitosa Teresa Ferreira Krista Fischer Pierre Fontanillas Ross M Fraser Daniel F Freitag Deepti Gurdasani Kauko Heikkilä Elina Hyppönen Aaron Isaacs Anne U Jackson Åsa Johansson Toby Johnson Marika Kaakinen Johannes Kettunen Marcus E Kleber Xiaohui Li Jian'an Luan Leo-Pekka Lyytikäinen Patrik K E Magnusson Massimo Mangino Evelin Mihailov May E Montasser Martina Müller-Nurasyid Ilja M Nolte Jeffrey R O'Connell Cameron D Palmer Markus Perola Ann-Kristin Petersen Serena Sanna Richa Saxena Susan K Service Sonia Shah Dmitry Shungin Carlo Sidore Ci Song Rona J Strawbridge Ida Surakka Toshiko Tanaka Tanya M Teslovich Gudmar Thorleifsson Evita G Van den Herik Benjamin F Voight Kelly A Volcik Lindsay L Waite Andrew Wong Ying Wu Weihua Zhang Devin Absher Gershim Asiki Inês Barroso Latonya F Been Jennifer L Bolton Lori L Bonnycastle Paolo Brambilla Mary S Burnett Giancarlo Cesana Maria Dimitriou Alex S F Doney Angela Döring Paul Elliott Stephen E Epstein Gudmundur Ingi Eyjolfsson Bruna Gigante Mark O Goodarzi Harald Grallert Martha L Gravito Christopher J Groves Göran Hallmans Anna-Liisa Hartikainen Caroline Hayward Dena Hernandez Andrew A Hicks Hilma Holm Yi-Jen Hung Thomas Illig Michelle R Jones Pontiano Kaleebu John J P Kastelein Kay-Tee Khaw Eric Kim Norman Klopp Pirjo Komulainen Meena Kumari Claudia Langenberg Terho Lehtimäki Shih-Yi Lin Jaana Lindström Ruth J F Loos François Mach Wendy L McArdle Christa Meisinger Braxton D Mitchell Gabrielle Müller Ramaiah Nagaraja Narisu Narisu Tuomo V M Nieminen Isleifur Olafsson Ken K Ong Aarno Palotie Theodore Papamarkou Cristina Pomilla Anneli Pouta Daniel J Rader Muredach P Reilly Paul M Ridker Fernando Rivadeneira Igor Rudan Aimo Ruokonen Nilesh Samani Hubert Scharnagl Janet Seeley Kaisa Silander Alena Stančáková Kathleen Stirrups Amy J Swift Laurence Tiret Andre G Uitterlinden L Joost van Pelt Sailaja Vedantam Nicholas Wainwright Cisca Wijmenga Sarah H Wild Gonneke Willemsen Tom Wilsgaard James F Wilson Elizabeth H Young Jing Hua Zhao Linda S Adair Dominique Arveiler Themistocles L Assimes Stefania Bandinelli Franklyn Bennett Murielle Bochud Bernhard O Boehm Dorret I Boomsma Ingrid B Borecki Stefan R Bornstein Pascal Bovet Michel Burnier Harry Campbell Aravinda Chakravarti John C Chambers Yii-Der Ida Chen Francis S Collins Richard S Cooper John Danesh George Dedoussis Ulf de Faire Alan B Feranil Jean Ferrières Luigi Ferrucci Nelson B Freimer Christian Gieger Leif C Groop Vilmundur Gudnason Ulf Gyllensten Anders Hamsten Tamara B Harris Aroon Hingorani Joel N Hirschhorn Albert Hofman G Kees Hovingh Chao Agnes Hsiung Steve E Humphries Steven C Hunt Kristian Hveem Carlos Iribarren Marjo-Riitta Järvelin Antti Jula Mika Kähönen Jaakko Kaprio Antero Kesäniemi Mika Kivimaki Jaspal S Kooner Peter J Koudstaal Ronald M Krauss Diana Kuh Johanna Kuusisto Kirsten O Kyvik Markku Laakso Timo A Lakka Lars Lind Cecilia M Lindgren Nicholas G Martin Winfried März Mark I McCarthy Colin A McKenzie Pierre Meneton Andres Metspalu Leena Moilanen Andrew D Morris Patricia B Munroe Inger Njølstad Nancy L Pedersen Chris Power Peter P Pramstaller Jackie F Price Bruce M Psaty Thomas Quertermous Rainer Rauramaa Danish Saleheen Veikko Salomaa Jouko Saramies Peter E H Schwarz Wayne H-H Sheu Alan R Shuldiner Agneta Siegbahn Tim D Spector Kari Stefansson David P Strachan Bamidele O Tayo Elena Tremoli Jaakko Tuomilehto Matti Uusitupa Cornelia M van Duijn Peter Vollenweider Lars Wallentin Nicholas J Wareham John B Whitfield Bruce H R Wolffenbuttel Jose M Ordovas Eric Boerwinkle Colin N A Palmer Unnur Thorsteinsdottir Daniel I Chasman Jerome I Rotter Paul W Franks Samuli Ripatti L Adrienne Cupples Manjinder S Sandhu Stephen S Rich Michael Boehnke Panos Deloukas Sekar Kathiresan Karen L Mohlke Erik Ingelsson Gonçalo R Abecasis

Nat Genet 2013 Nov 6;45(11):1274-1283. Epub 2013 Oct 6.

Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

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November 2013
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