Discovery and refinement of loci associated with lipid levels

发现和完善与脂质水平相关的基因位点

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作者：Willer,Cristen J,Schmidt,Ellen M,Sengupta,Sebanti,Peloso,Gina M,Gustafsson,Stefan,Kanoni,Stavroula,Ganna,Andrea,Chen,Jin,Buchkovich,Martin L,Mora,Samia,Beckmann,Jacques S,Bragg-Gresham,Jennifer L,Chang,Hsing-Yi,Demirkan,Ayşe,Den Hertog,Heleen M,Do,Ron,Donnelly,Louise A,Ehret,Georg B,Esko,Tõnu,Feitosa,Mary F,Ferreira,Teresa,Fischer,Krista,Fontanillas,Pierre,Fraser,Ross M,Freitag,Daniel F,Gurdasani,Deepti,Heikkilä,Kauko,Hyppönen,Elina,Isaacs,Aaron,Jackson,Anne U,Johansson,Åsa,Johnson,Toby,Kaakinen,Marika,Kettunen,Johannes,Kleber,Marcus E,Li,Xiaohui,Luan,Jian'an,Lyytikäinen,Leo-Pekka,Magnusson,Patrik K E,Mangino,Massimo,Mihailov,Evelin,Montasser,May E,Müller-Nurasyid,Martina,Nolte,Ilja M,O'Connell,Jeffrey R,Palmer,Cameron D,Perola,Markus,Petersen,Ann-Kristin,Sanna,Serena,Saxena,Richa,Service,Susan K,Shah,Sonia,Shungin,Dmitry,Sidore,Carlo,Song,Ci,Strawbridge,Rona J,Surakka,Ida,Tanaka,Toshiko,Teslovich,Tanya M,Thorleifsson,Gudmar,Van den Herik,Evita G,Voight,Benjamin F,Volcik,Kelly A,Waite,Lindsay L,Wong,Andrew,Wu,Ying,Zhang,Weihua,Absher,Devin,Asiki,Gershim,Barroso,Inês,Been,Latonya F,Bolton,Jennifer L,Bonnycastle,Lori L,Brambilla,Paolo,Burnett,Mary S,Cesana,Giancarlo,Dimitriou,Maria,Doney,Alex S F,Döring,Angela,Elliott,Paul,Epstein,Stephen E,Ingi Eyjolfsson,Gudmundur,Gigante,Bruna,Goodarzi,Mark O,Grallert,Harald,Gravito,Martha L,Groves,Christopher J,Hallmans,Göran,Hartikainen,Anna-Liisa,Hayward,Caroline,Hernandez,Dena,Hicks,Andrew A,Holm,Hilma,Hung,Yi-Jen,Illig,Thomas,Jones,Michelle R,Kaleebu,Pontiano,Kastelein,John J P,Khaw,Kay-Tee,Kim,Eric,Klopp,Norman,Komulainen,Pirjo,Kumari,Meena,Langenberg,Claudia,Lehtimäki,Terho,Lin,Shih-Yi,Lindström,Jaana,Loos,Ruth J F,Mach,François,McArdle,Wendy L,Meisinger,Christa,Mitchell,Braxton D,Müller,Gabrielle,Nagaraja,Ramaiah,Narisu,Narisu,Nieminen,Tuomo V M,Nsubuga,Rebecca N,Olafsson,Isleifur,Ong,Ken K,Palotie,Aarno,Papamarkou,Theodore,Pomilla,Cristina,Pouta,Anneli,Rader,Daniel J,Reilly,Muredach P,Ridker,Paul M,Rivadeneira,Fernando,Rudan,Igor,Ruokonen,Aimo,Samani,Nilesh,Scharnagl,Hubert,Seeley,Janet,Silander,Kaisa,Stančáková,Alena,Stirrups,Kathleen,Swift,Amy J,Tiret,Laurence,Uitterlinden,Andre G,van Pelt,L Joost,Vedantam,Sailaja,Wainwright,Nicholas,Wijmenga,Cisca,Wild,Sarah H,Willemsen,Gonneke,Wilsgaard,Tom,Wilson,James F,Young,Elizabeth H,Zhao,Jing Hua,Adair,Linda S,Arveiler,Dominique,Assimes,Themistocles L,Bandinelli,Stefania,Bennett,Franklyn,Bochud,Murielle,Boehm,Bernhard O,Boomsma,Dorret I,Borecki,Ingrid B,Bornstein,Stefan R,Bovet,Pascal,Burnier,Michel,Campbell,Harry,Chakravarti,Aravinda,Chambers,John C,Chen,Yii-Der Ida,Collins,Francis S,Cooper,Richard S,Danesh,John,Dedoussis,George,de Faire,Ulf,Feranil,Alan B,Ferrières,Jean,Ferrucci,Luigi,Freimer,Nelson B,Gieger,Christian,Groop,Leif C,Gudnason,Vilmundur,Gyllensten,Ulf,Hamsten,Anders,Harris,Tamara B,Hingorani,Aroon,Hirschhorn,Joel N,Hofman,Albert,Hovingh,G Kees,Hsiung,Chao Agnes,Humphries,Steve E,Hunt,Steven C,Hveem,Kristian,Iribarren,Carlos,Järvelin,Marjo-Riitta,Jula,Antti,Kähönen,Mika,Kaprio,Jaakko,Kesäniemi,Antero,Kivimaki,Mika,Kooner,Jaspal S,Koudstaal,Peter J,Krauss,Ronald M,Kuh,Diana,Kuusisto,Johanna,Kyvik,Kirsten O,Laakso,Markku,Lakka,Timo A,Lind,Lars,Lindgren,Cecilia M,Martin,Nicholas G,März,Winfried,McCarthy,Mark I,McKenzie,Colin A,Meneton,Pierre,Metspalu,Andres,Moilanen,Leena,Morris,Andrew D,Munroe,Patricia B,Njølstad,Inger,Pedersen,Nancy L,Power,Chris,Pramstaller,Peter P,Price,Jackie F,Psaty,Bruce M,Quertermous,Thomas,Rauramaa,Rainer,Saleheen,Danish,Salomaa,Veikko,Sanghera,Dharambir K,Saramies,Jouko,Schwarz,Peter E H,Sheu,Wayne H-H,Shuldiner,Alan R,Siegbahn,Agneta,Spector,Tim D,Stefansson,Kari,Strachan,David P,Tayo,Bamidele O,Tremoli,Elena,Tuomilehto,Jaakko,Uusitupa,Matti,van Duijn,Cornelia M,Vollenweider,Peter,Wallentin,Lars,Wareham,Nicholas J,Whitfield,John B,Wolffenbuttel,Bruce H R,Ordovas,Jose M,Boerwinkle,Eric,Palmer,Colin N A,Thorsteinsdottir,Unnur,Chasman,Daniel I,Rotter,Jerome I,Franks,Paul W,Ripatti,Samuli,Cupples,L Adrienne,Sandhu,Manjinder S,Rich,Stephen S,Boehnke,Michael,Deloukas,Panos,Kathiresan,Sekar,Mohlke,Karen L,Ingelsson,Erik,Abecasis,Gonçalo R
期刊：Nature Genetics影响因子：29.000
时间：2013起止号：2013 Nov;45(11):1274-1283
doi：10.1038/ng.2797

Abstract

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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