New genetic loci link adipose and insulin biology to body fat distribution

新的基因位点将脂肪和胰岛素生物学与体脂分布联系起来

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作者：Shungin,Dmitry,Winkler,Thomas W,Croteau-Chonka,Damien C,Ferreira,Teresa,Locke,Adam E,Mägi,Reedik,Strawbridge,Rona J,Pers,Tune H,Fischer,Krista,Justice,Anne E,Workalemahu,Tsegaselassie,Wu,Joseph M W,Buchkovich,Martin L,Heard-Costa,Nancy L,Roman,Tamara S,Drong,Alexander W,Song,Ci,Gustafsson,Stefan,Day,Felix R,Esko,Tonu,Fall,Tove,Kutalik,Zoltán,Luan,Jian'an,Randall,Joshua C,Scherag,André,Vedantam,Sailaja,Wood,Andrew R,Chen,Jin,Fehrmann,Rudolf,Karjalainen,Juha,Kahali,Bratati,Liu,Ching-Ti,Schmidt,Ellen M,Absher,Devin,Amin,Najaf,Anderson,Denise,Beekman,Marian,Bragg-Gresham,Jennifer L,Buyske,Steven,Demirkan,Ayse,Ehret,Georg B,Feitosa,Mary F,Goel,Anuj,Jackson,Anne U,Johnson,Toby,Kleber,Marcus E,Kristiansson,Kati,Mangino,Massimo,Leach,Irene Mateo,Medina-Gomez,Carolina,Palmer,Cameron D,Pasko,Dorota,Pechlivanis,Sonali,Peters,Marjolein J,Prokopenko,Inga,Stančáková,Alena,Sung,Yun Ju,Tanaka,Toshiko,Teumer,Alexander,Van Vliet-Ostaptchouk,Jana V,Yengo,Loïc,Zhang,Weihua,Albrecht,Eva,Ärnlöv,Johan,Arscott,Gillian M,Bandinelli,Stefania,Barrett,Amy,Bellis,Claire,Bennett,Amanda J,Berne,Christian,Blüher,Matthias,Böhringer,Stefan,Bonnet,Fabrice,Böttcher,Yvonne,Bruinenberg,Marcel,Carba,Delia B,Caspersen,Ida H,Clarke,Robert,Daw,E Warwick,Deelen,Joris,Deelman,Ewa,Delgado,Graciela,Doney,Alex Sf,Eklund,Niina,Erdos,Michael R,Estrada,Karol,Eury,Elodie,Friedrich,Nele,Garcia,Melissa E,Giedraitis,Vilmantas,Gigante,Bruna,Go,Alan S,Golay,Alain,Grallert,Harald,Grammer,Tanja B,Gräßler,Jürgen,Grewal,Jagvir,Groves,Christopher J,Haller,Toomas,Hallmans,Goran,Hartman,Catharina A,Hassinen,Maija,Hayward,Caroline,Heikkilä,Kauko,Herzig,Karl-Heinz,Helmer,Quinta,Hillege,Hans L,Holmen,Oddgeir,Hunt,Steven C,Isaacs,Aaron,Ittermann,Till,James,Alan L,Johansson,Ingegerd,Juliusdottir,Thorhildur,Kalafati,Ioanna-Panagiota,Kinnunen,Leena,Koenig,Wolfgang,Kooner,Ishminder K,Kratzer,Wolfgang,Lamina,Claudia,Leander,Karin,Lee,Nanette R,Lichtner,Peter,Lind,Lars,Lindström,Jaana,Lobbens,Stéphane,Lorentzon,Mattias,Mach,François,Magnusson,Patrik Ke,Mahajan,Anubha,McArdle,Wendy L,Menni,Cristina,Merger,Sigrun,Mihailov,Evelin,Milani,Lili,Mills,Rebecca,Moayyeri,Alireza,Monda,Keri L,Mooijaart,Simon P,Mühleisen,Thomas W,Mulas,Antonella,Müller,Gabriele,Müller-Nurasyid,Martina,Nagaraja,Ramaiah,Nalls,Michael A,Narisu,Narisu,Glorioso,Nicola,Nolte,Ilja M,Olden,Matthias,Rayner,Nigel W,Renstrom,Frida,Ried,Janina S,Robertson,Neil R,Rose,Lynda M,Sanna,Serena,Scharnagl,Hubert,Scholtens,Salome,Sennblad,Bengt,Seufferlein,Thomas,Sitlani,Colleen M,Smith,Albert Vernon,Stirrups,Kathleen,Stringham,Heather M,Sundström,Johan,Swertz,Morris A,Swift,Amy J,Syvänen,Ann-Christine,Tayo,Bamidele O,Thorand,Barbara,Thorleifsson,Gudmar,Tomaschitz,Andreas,Troffa,Chiara,van Oort,Floor Va,Verweij,Niek,Vonk,Judith M,Waite,Lindsay L,Wennauer,Roman,Wilsgaard,Tom,Wojczynski,Mary K,Wong,Andrew,Zhang,Qunyuan,Zhao,Jing Hua,Brennan,Eoin P,Choi,Murim,Eriksson,Per,Folkersen,Lasse,Franco-Cereceda,Anders,Gharavi,Ali G,Hedman,Åsa K,Hivert,Marie-France,Huang,Jinyan,Kanoni,Stavroula,Karpe,Fredrik,Keildson,Sarah,Kiryluk,Krzysztof,Liang,Liming,Lifton,Richard P,Ma,Baoshan,McKnight,Amy J,McPherson,Ruth,Metspalu,Andres,Min,Josine L,Moffatt,Miriam F,Montgomery,Grant W,Murabito,Joanne M,Nicholson,George,Nyholt,Dale R,Olsson,Christian,Perry,John Rb,Reinmaa,Eva,Salem,Rany M,Sandholm,Niina,Schadt,Eric E,Scott,Robert A,Stolk,Lisette,Vallejo,Edgar E,Westra,Harm-Jan,Zondervan,Krina T,Amouyel,Philippe,Arveiler,Dominique,Bakker,Stephan Jl,Beilby,John,Bergman,Richard N,Blangero,John,Brown,Morris J,Burnier,Michel,Campbell,Harry,Chakravarti,Aravinda,Chines,Peter S,Claudi-Boehm,Simone,Collins,Francis S,Crawford,Dana C,Danesh,John,de Faire,Ulf,de Geus,Eco Jc,Dörr,Marcus,Erbel,Raimund,Eriksson,Johan G,Farrall,Martin,Ferrannini,Ele,Ferrières,Jean,Forouhi,Nita G,Forrester,Terrence,Franco,Oscar H,Gansevoort,Ron T,Gieger,Christian,Gudnason,Vilmundur,Haiman,Christopher A,Harris,Tamara B,Hattersley,Andrew T,Heliövaara,Markku,Hicks,Andrew A,Hingorani,Aroon D,Hoffmann,Wolfgang,Hofman,Albert,Homuth,Georg,Humphries,Steve E,Hyppönen,Elina,Illig,Thomas,Jarvelin,Marjo-Riitta,Johansen,Berit,Jousilahti,Pekka,Jula,Antti M,Kaprio,Jaakko,Kee,Frank,Keinanen-Kiukaanniemi,Sirkka M,Kooner,Jaspal S,Kooperberg,Charles,Kovacs,Peter,Kraja,Aldi T,Kumari,Meena,Kuulasmaa,Kari,Kuusisto,Johanna,Lakka,Timo A,Langenberg,Claudia,Le Marchand,Loic,Lehtimäki,Terho,Lyssenko,Valeriya,Männistö,Satu,Marette,André,Matise,Tara C,McKenzie,Colin A,McKnight,Barbara,Musk,Arthur W,Möhlenkamp,Stefan,Morris,Andrew D,Nelis,Mari,Ohlsson,Claes,Oldehinkel,Albertine J,Ong,Ken K,Palmer,Lyle J,Penninx,Brenda W,Peters,Annette,Pramstaller,Peter P,Raitakari,Olli T,Rankinen,Tuomo,Rao,D C,Rice,Treva K,Ridker,Paul M,Ritchie,Marylyn D,Rudan,Igor,Salomaa,Veikko,Samani,Nilesh J,Saramies,Jouko,Sarzynski,Mark A,Schwarz,Peter Eh,Shuldiner,Alan R,Staessen,Jan A,Steinthorsdottir,Valgerdur,Stolk,Ronald P,Strauch,Konstantin,Tönjes,Anke,Tremblay,Angelo,Tremoli,Elena,Vohl,Marie-Claude,Völker,Uwe,Vollenweider,Peter,Wilson,James F,Witteman,Jacqueline C,Adair,Linda S,Bochud,Murielle,Boehm,Bernhard O,Bornstein,Stefan R,Bouchard,Claude,Cauchi,Stéphane,Caulfield,Mark J,Chambers,John C,Chasman,Daniel I,Cooper,Richard S,Dedoussis,George,Ferrucci,Luigi,Froguel,Philippe,Grabe,Hans-Jörgen,Hamsten,Anders,Hui,Jennie,Hveem,Kristian,Jöckel,Karl-Heinz,Kivimaki,Mika,Kuh,Diana,Laakso,Markku,Liu,Yongmei,März,Winfried,Munroe,Patricia B,Njølstad,Inger,Oostra,Ben A,Palmer,Colin Na,Pedersen,Nancy L,Perola,Markus,Pérusse,Louis,Peters,Ulrike,Power,Chris,Quertermous,Thomas,Rauramaa,Rainer,Rivadeneira,Fernando,Saaristo,Timo E,Saleheen,Danish,Sinisalo,Juha,Slagboom,P Eline,Snieder,Harold,Spector,Tim D,Stefansson,Kari,Stumvoll,Michael,Tuomilehto,Jaakko,Uitterlinden,André G,Uusitupa,Matti,van der Harst,Pim,Veronesi,Giovanni,Walker,Mark,Wareham,Nicholas J,Watkins,Hugh,Wichmann,H-Erich,Abecasis,Goncalo R,Assimes,Themistocles L,Berndt,Sonja I,Boehnke,Michael,Borecki,Ingrid B,Deloukas,Panos,Franke,Lude,Frayling,Timothy M,Groop,Leif C,Hunter,David J,Kaplan,Robert C,O'Connell,Jeffrey R,Qi,Lu,Schlessinger,David,Strachan,David P,Thorsteinsdottir,Unnur,van Duijn,Cornelia M,Willer,Cristen J,Visscher,Peter M,Yang,Jian,Hirschhorn,Joel N,Zillikens,M Carola,McCarthy,Mark I,Speliotes,Elizabeth K,North,Kari E,Fox,Caroline S,Barroso,Inês,Franks,Paul W,Ingelsson,Erik,Heid,Iris M,Loos,Ruth Jf,Cupples,L Adrienne,Morris,Andrew P,Lindgren,Cecilia M,Mohlke,Karen L
期刊：Nature影响因子：48.500
时间：2015起止号：2015 Feb 12;518(7538):187-196
doi：10.1038/nature14132研究方向： 免疫/内分泌

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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