Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering.
Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering.
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作者：
Powe CE;Udler MS;Hsu S;Allard C;Kuang A;Manning AK;Perron P;Bouchard L;Lowe WL Jr;Scholtens D;Florez JC;Hivert MF
数以百计的常见遗传变异通过不同的生理途径影响患2型糖尿病(T2D)的风险。目前尚不清楚妊娠期糖尿病(GDM)的生理基础与T2D有多大的不同。在这项对来自三个队列的5,000名孕妇的研究中，我们的目标是使用两种基于贝叶斯非负矩阵因式(BNMF)聚类的互补方法来识别与GDM相关的生理相关的母体变异组。首先，我们测试了五个母体T2D相关变异的bNMF簇，这些变异根据孕外生理进行分组，以确定是否与妊娠期糖尿病有关。我们发现，代表β细胞功能降低和肝脂代谢异常的遗传决定因素的聚集性多基因得分与妊娠期糖尿病相关；这些聚集性与婴儿出生体重无关。其次，我们根据妊娠生理学得出了母体变异的bNMF簇，并测试了这些簇与妊娠期糖尿病的相关性。我们确定了一个与妊娠期糖尿病以及较高的婴儿出生体重密切相关的簇。该星团与GDM的关联的影响大小似乎大于T2D。我们的发现表明，导致妊娠期糖尿病的遗传和生理途径至少在一定程度上与导致T2D的不同。
Hundreds of common genetic variants acting through distinguishable physiologic pathways influence the risk of type 2 diabetes (T2D). It is unknown to what extent the physiology underlying gestational diabetes mellitus (GDM) is distinct from that underlying T2D. In this study of >5,000 pregnant women from three cohorts, we aimed to identify physiologically related groups of maternal variants associated with GDM using two complementary approaches that were based on Bayesian nonnegative matrix factorization (bNMF) clustering. First, we tested five bNMF clusters of maternal T2D-associated variants grouped on the basis of physiology outside of pregnancy for association with GDM. We found that cluster polygenic scores representing genetic determinants of reduced β-cell function and abnormal hepatic lipid metabolism were associated with GDM; these clusters were not associated with infant birth weight. Second, we derived bNMF clusters of maternal variants on the basis of pregnancy physiology and tested these clusters for association with GDM. We identified a cluster that was strongly associated with GDM as well as associated with higher infant birth weight. The effect size for this cluster’s association with GDM appeared greater than that for T2D. Our findings imply that the genetic and physiologic pathways that lead to GDM differ, at least in part, from those that lead to T2D.
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影响因子：
30.8
作者：
Mahajan A;Taliun D;Thurner M;Robertson NR;Torres JM;Rayner NW;Payne AJ;Steinthorsdottir V;Scott RA;Grarup N;Cook JP;Schmidt EM;Wuttke M;Sarnowski C;Mägi R;Nano J;Gieger C;Trompet S;Lecoeur C;Preuss MH;Prins BP;Guo X;Bielak LF;Below JE;Bowden DW;Chambers JC;Kim YJ;Ng MCY;Petty LE;Sim X;Zhang W;Bennett AJ;Bork-Jensen J;Brummett CM;Canouil M;Ec Kardt KU;Fischer K;Kardia SLR;Kronenberg F;Läll K;Liu CT;Locke AE;Luan J;Ntalla I;Nylander V;Schönherr S;Schurmann C;Yengo L;Bottinger EP;Brandslund I;Christensen C;Dedoussis G;Florez JC;Ford I;Franco OH;Frayling TM;Giedraitis V;Hackinger S;Hattersley AT;Herder C;Ikram MA;Ingelsson M;Jørgensen ME;Jørgensen T;Kriebel J;Kuusisto J;Ligthart S;Lindgren CM;Linneberg A;Lyssenko V;Mamakou V;Meitinger T;Mohlke KL;Morris AD;Nadkarni G;Pankow JS;Peters A;Sattar N;Stančáková A;Strauch K;Taylor KD;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tuomilehto J;Witte DR;Dupuis J;Peyser PA;Zeggini E;Loos RJF;Froguel P;Ingelsson E;Lind L;Groop L;Laakso M;Collins FS;Jukema JW;Palmer CNA;Grallert H;Metspalu A;Dehghan A;Köttgen A;Abecasis GR;Meigs JB;Rotter JI;Marchini J;Pedersen O;Hansen T;Langenberg C;Wareham NJ;Stefansson K;Gloyn AL;Morris AP;Boehnke M;McCarthy MI
通讯作者：
McCarthy MI
影响因子：
7.7
作者：
Kwak SH;Kim SH;Cho YM;Go MJ;Cho YS;Choi SH;Moon MK;Jung HS;Shin HD;Kang HM;Cho NH;Lee IK;Kim SY;Han BG;Jang HC;Park KS
通讯作者：
Park KS
影响因子：
--
作者：
Karlson, Elizabeth W.;Boutin, Natalie T.;Allen, Nicole L.
通讯作者：
Allen, Nicole L.
影响因子：
81.5
作者：
McIntyre, H. David;Catalano, Patrick;Damm, Peter
通讯作者：
Damm, Peter
影响因子：
64.8
作者：
Locke, Adam E.;Kahali, Bratati;Berndt, Sonja I.;Justice, Anne E.;Pers, Tune H.;Day, Felix R.;Powell, Corey;Vedantam, Sailaja;Buchkovich, Martin L.;Yang, Jian;Croteau-Chonka, Damien C.;Esko, Tonu;Fall, Tove;Ferreira, Teresa;Gustafsson, Stefan;Kutalik, Zoltan;Luan, Jian'an;Maegi, Reedik;Randall, Joshua C.;Winkler, Thomas W.;Wood, Andrew R.;Workalemahu, Tsegaselassie;Faul, Jessica D.;Smith, Jennifer A.;Zhao, Jing Hua;Zhao, Wei;Chen, Jin;Fehrmann, Rudolf;Hedman, Asa K.;Karjalainen, Juha;Schmidt, Ellen M.;Absher, Devin;Amin, Najaf;Anderson, Denise;Beekman, Marian;Bolton, Jennifer L.;Bragg-Gresham, L.;Buyske, Steven;Demirkan, Ayse;Deng, Guohong;Ehret, Georg B.;Feenstra, Bjarke;Feitosa, Mary F.;Fischer, Krista;Goel, Anuj;Gong, Jian;Jackson, Anne U.;Kanoni, Stavroula;Kleber, Marcus E.;Kristiansson, Kati;Lim, Unhee;Lotay, Vaneet;Mangino, Massimo;Leach, Irene Mateo;Medina-Gomez, Carolina;Medland, Sarah E.;Nalls, Michael A.;Palmer, Cameron D.;Pasko, Dorota;Pechlivanis, Sonali;Peters, Marjolein J.;Prokopenko, Inga;Shungin, Dmitry;Stancakova, Alena;Strawbridge, Rona J.;Sung, Yun Ju;Tanaka, Toshiko;Teumer, Alexander;Trompet, Stella;van der Laan, Sander W.;van Settee, Jessica;Van Vliet-Ostaptchouk, Jana V.;Wang, Zhaoming;Yengo, Loic;Zhang, Weihua;Isaacs, Aaron;Albrecht, Eva;Arnlov, Johan;Arscott, Gillian M.;Attwood, Antony P.;Bandinelli, Stefania;Barrett, Amy;Bas, Isabelita N.;Bellis, Claire;Bennett, Amanda J.;Berne, Christian;Blagieva, Roza;Blueher, Matthias;Bohringer, Stefan;Bonnycastle, Lori L.;Boettcher, Yvonne;Boyd, Heather A.;Bruinenberg, Marcel;Caspersen, Ida H.;Chen, Yii-Der Ida;Clarke, Robert;Daw, E. Warwick;de Craen, Anton J. M.;Delgado, Graciela;Dimitriou, Maria;Doney, Alex S. F.;Eklund, Niina;Estrada, Karol;Eury, Elodie;Folkersen, Lasse;Fraser, Ross M.;Garcia, Melissa E.;Geller, Frank;Giedraitis, Vilmantas;Gigante, Bruna;Go, Alan S.;Golay, Alain;Goodall, Alison H.;Gordon, Scott D.;Gorski, Mathias;Grabe, Hans-Joergen;Grallert, Harald;Grammer, Tanja B.;Graessler, Jurgen;Gronberg, Henrik;Groves, Christopher J.;Gusto, Gaeelle;Haessler, Jeffrey;Hall, Per;Haller, Toomas;Hallmans, Goran;Hartman, Catharina A.;Hassinen, Maija;Hayward, Caroline;Heard-Costa, Nancy L.;Helmer, Qinta;Hengstenberg, Christian;Holmen, Oddgeir;Hottenga, Jouke-Jan;James, Alan L.;Jeff, Janina M.;Johansson, Asa;Jolley, Jennifer;Juliusdottir, Thorhildur;Kinnunen, Leena;Koenig, Wolfgang;Koskenvuo, Markku;Kratzer, Wolfgang;Laitinen, Jaana;Lamina, Claudia;Leander, Karin;Lee, Nanette R.;Lichtner, Peter;Lind, Lars;Lindstrom, Jaana;Lo, Ken Sin;Lobbens, Stephane;Lorbeer, Roberto;Lu, Yingchang;Mach, Francois;Magnusson, Patrik K. E.;Mahajan, Anubha;McArdle, Wendy L.;McLachlan, Stela;Menni, Cristina;Merger, Sigrun;Mihailov, Evelin;Milani, Lili;Moayyeri, Alireza;Monda, Keri L.;Morken, Mario A.;Mulas, Antonella;Mueller, Gabriele;Mueller-Nurasyid, Martina;Musk, Arthur W.;Nagaraja, Ramaiah;Noethen, Markus M.;Nolte, Ilja M.;Pilz, Stefan;Rayner, Nigel W.;Renstrom, Frida;Rettig, Rainer;Ried, Janina S.;Ripke, Stephan;Robertson, Neil R.;Rose, Lynda M.;Sanna, Serena;Scharnagl, Hubert;Scholtens, Salome;Schumacher, Fredrick R.;Scott, William R.;Seufferlein, Thomas;Shi, Jianxin;Smith, Albert Vernon;Smolonska, Joanna;Stanton, Alice V.;Steinthorsdottir, Valgerdur;Stirrups, Kathleen;Stringham, Heather M.;Sundstrom, Johan;Swertz, Morris A.;Swift, Amy J.;Syvanen, Ann-Christine;Tan, Sian-Tsung;Tayo, Bamidele O.;Thorand, Barbara;Thorleifsson, Gudmar;Tyrer, Jonathan P.;Uh, Hae-Won;Vandenput, Liesbeth;Verhulst, Frank C.;Vermeulen, Sita H.;Verweij, Niek;Vonk, Judith M.;Waite, Lindsay L.;Warren, Helen R.;Waterworth, Dawn;Weedon, Michael N.;Wilkens, Lynne R.;Willenborg, Christina;Wilsgaard, Tom;Wojczynski, Mary K.;Wong, Andrew;Wrightl, Alan F.;Zhang, Qunyuan;Brennan, Eoin P.;Choi, Murim;Dastani, Zari;Drong, Alexander W.;Eriksson, Per;Franco-Cereceda, Anders;Gadin, Jesper R.;Gharavi, Ali G.;Goddard, Michael E.;Handsaker, Robert E.;Huang, Jinyan;Karpe, Fredrik;Kathiresan, Sekar;Keildson, Sarah;Kiryluk, Krzysztof;Kubo, Michiaki;Lee, Jong-Young;Liang, Liming;Lifton, Richard P.;Ma, Baoshan;McCarroll, Steven A.;McKnight, Amy J.;Min, Josine L.;Moffatt, Miriam F.;Montgomery, Grant W.;Murabito, Joanne M.;Nicholson, George;Nyholt, Dale R.;Okada, Yukinori;Perry, John R. B.;Dorajoo, Rajkumar;Reinmaa, Eva;Salem, Rany M.;Sandholm, Niina;Scott, Robert A.;Stolk, Lisette;Takahashi, Atsushi;Tanaka, Toshihiro;van 't Hooft, Ferdinand M.;Vinkhuyzen, Anna A. E.;Westra, Harm-Jan;Zheng, Wei;Zondervan, Krina T.;Heath, Andrew C.;Arveiler, Dominique;Bakker, Stephan J. L.;Beilby, John;Bergman, Richard N.;Blangero, John;Bovet, Pascal;Campbell, Harry;Caulfield, Mark J.;Cesana, Giancarlo;Chakravarti, Aravinda;Chasman, Daniel I.;Chines, Peter S.;Collins, Francis S.;Crawford, Dana C.;Cupples, L. Adrienne;Cusi, Daniele;Danesh, John;de Faire, Ulf;den Ruijter, Hester M.;Dominiczak, Anna F.;Erbel, Raimund;Erdmann, Jeanette;Eriksson, Johan G.;Farrall, Martin;Felix, Stephan B.;Ferrannini, Ele;Ferrieres, Jean;Ford, Ian;Forouhi, Nita G.;Forrester, Terrence;Franco, Oscar H.;Gansevoort, Ron T.;Gejman, Pablo V.;Gieger, Christian;Gottesman, Omri;Gudnason, Vilmundur;Gyllensten, Ulf;Hall, Alistair S.;Harris, Tamara B.;Hattersley, Andrew T.;Hicks, Andrew A.;Hindorff, Lucia A.;Hingorani, Aroon D.;Hofman, Albert;Homuth, Georg;Hovingh, G. Kees;Humphries, Steve E.;Hunt, Steven C.;Hypponen, Elina;Illig, Thomas;Jacobs, Kevin B.;Jarvelin, Marjo-Riitta;Joeckel, Karl-Heinz;Johansen, Berit;Jousilahti, Pekka;Jukema, J. Wouter;Jula, Antti M.;Kaprio, Jaakko;Kastelein, John J. P.;Keinanen-Kiukaanniemi, Sirkka M.;Kiemeney, Lambertus A.;Knekt, Paul;Kooner, Jaspal S.;Kooperberg, Charles;Kovacs, Peter;Kraja, Aldi T.;Kumari, Meena;Kuusisto, Johanna;Lakka, Timo A.;Langenberg, Claudia;Le Marchand, Laic;Lehtimaki, Terho;Lyssenko, Valeriya;Mannisto, Satu;Marette, Andre;Matise, Tara C.;McKenzie, Colin A.;McKnight, Barbara;Moll, Frans L.;Morris, Andrew D.;Morris, Andrew P.;Murray, Jeffrey C.;Nelis, Mari;Ohlsson, Claes;Oldehinkel, Albertine J.;Ong, Ken K.;Madden, Pamela A. F.;Pasterkamp, Gerard;Peden, John F.;Peters, Annette;Postma, Dirkje S.;Pramstaller, Peter P.;Price, Jackie F.;Qi, Lu;Raitakari, Olli T.;Rankinen, Tuomo;Rao, D. C.;Rice, Treva K.;Ridker, Paul M.;Rioux, John D.;Ritchie, Marylyn D.;Rudan, Igor;Salomaa, Veikko;Samani, Nilesh J.;Saramines, Jouko;Sarzynski, Mark A.;Schunkert, Heribert;Schwarz, Peter E. H.;Sever, Peter;Shuldiner, Alan R.;Sinisalo, Juha;Stolk, Ronald P.;Strauch, Konstantin;Toenjes, Anke;Tregouet, David-Alexandre;Tremblay, Angelo;Tremoli, Elena;Virtamo, Jarmo;Vohl, Marie-Claude;Voelker, Uwe;Waeber, Gerard;Willemsen, Gonneke;Witteman, Jacqueline C.;Zillikens, M. Carola;Adair, Linda S.;Amouyel, Philippe;Asselbergs, Folkert W.;Assimes, Themistocles L.;Bochud, Murielle;Boehm, Bernhard O.;Boerwinkle, Eric;Bornstein, Stefan R.;Bottinger, Erwin P.;Bouchard, Claude;Cauchi, Stephane;Chambers, John C.;Chanock, Stephen J.;Cooper, Richard S.;de Bakker, Paul I. W.;Dedoussis, George;Ferrucci, Luigi;Franks, Paul W.;Froguel, Philippe;Groop, Leif C.;Haiman, Christopher A.;Hamsten, Anders;Hui, Jennie;Hunter, David J.;Hveem, Kristian;Kaplan, Robert C.;Kivimaki, Mika;Kuh, Diana;Laakso, Markku;Liu, Yongmei;Martin, Nicholas G.;Maerz, Winfried;Melbve, Mads;Metspalu, Andres;Moebus, Susanne;Munroe, Patricia B.;Njolstad, Inger;Oostra, Ben A.;Palmer, Colin N. A.;Pedersen, Nancy L.;Perola, Markus;Perusse, Louis;Peters, Ulrike;Power, Chris;Quertermous, Thomas;Rauramaa, Rainer;Rivadeneira, Fernando;Saaristo, Timo E.;Saleheen, Danish;Sattar, Naveed;Schadt, Eric E.;Schlessinger, David;Slagboom, P. Eline;Snieder, Harold;Spector, Tim D.;Thorsteinsdottir, Unnu R.;Stumvoll, Michael;Tuomilehto, Jaakko;Uitterlinden, Andre G.;Uusitupa, Matti;van der Harst, Pim;Walker, Mark;Wallaschofski, Henri;Wareham, Nicholas J.;Watkins, Hugh;Weir, David R.;Wichmann, H-Erich;Wilson, James F.;Zanen, Pieter;Borecki, Ingrid B.;Deloukas, Panos;Fox, Caroline S.;Heid, Iris M.;O'Connell, Jeffrey R.;Strachan, David P.;Stefansson, Kari;van Duijri, Cornelia M.;Abecasis, Goncalo R.;Franke, Lude;Frayling, Timothy M.;McCarthy, Mark I.;Visscher, Peter M.;Scherag, Andre;Willer, Cristen J.;Boehnke, Michael;Mohlke, Karen L.;Lindgren, Cecilia M.;Beckmann, Jacques S.;Barroso, Ines;North, Kari E.;Ingelsson, Erik;Hirschhorn, Joel N.;Loos, Ruth J. F.;Speliotes, Elizabeth K.
通讯作者：
Speliotes, Elizabeth K.