Thwart your destiny; effect of nonacoholic fatty liver disease genes on steatosis, liver injury and cirrhosis varies by body mass index.
Thwart your destiny; effect of nonacoholic fatty liver disease genes on steatosis, liver injury and cirrhosis varies by body mass index.
复制标题
DOI：
10.1002/hep.29739
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Speliotes EK
中科院分区：
文献类型：
--
作者：
Speliotes EK
大多数常见的人类疾病是由于内在风险与接触的结合而形成的。换句话说，这些疾病归因于遗传风险与环境触发因素的结合。非酒精性脂肪肝（NAFLD）也不例外。遗传和环境变量都与NAFLD有关。然而，最近的一篇文章超越了这些关联，了解了遗传风险变异背景下的环境暴露如何加剧NAFLD的发展。遗传关联研究通常假设一个加性遗传模型来评估与疾病的关联。这转化为一个模型，其中具有遗传变异的0，1或2个等位基因线性增加疾病的风险。然而，在某些情况下，这些相同的等位基因不是增加风险，而是增加风险。也就是说，具有0、1或2个等位基因在一组条件（体重指数[BMI]< 25 kg/m2）下将风险增加1至2至4，并且在另一组条件（BMI> 35 kg/m2）下将风险增加1至8至16（图1A）。相同基因型的效应发生变化的条件称为修饰因子。识别遗传风险的环境修饰因子可以通过寻找基因环境相互作用来完成。识别疾病的修饰因子是重要的，因为如果修饰因子可以改变，则可以优先且显著地减轻疾病发展的遗传风险增加。Stender等人最近的一篇文章。(1)研究了肥胖对个体发生NAFLD风险的影响，这些个体携带编码马铃薯糖样磷脂酶结构域3（PNPLA 3）p.I148M（148位异亮氨酸至甲硫氨酸）、TM 6SF 2（跨膜6超家族成员2）p.E167K（167位谷氨酸至赖氨酸）和GCKR（葡萄糖激酶调节剂）的遗传变异体。
Most common human diseases develop because of a combination of endogenous risk combined with exposures. Said another way, these diseases are attributed to genetic risk combined with environmental triggers. Nonalcoholic fatty liver disease (NAFLD) is no exception. There have been both genetic and environmental variables that have been associated with NAFLD. One recent article, however, goes beyond these associations to understand how environmental exposures in the setting of genetic risk variants can exacerbate the development of NAFLD.Genetic associations studies usually assume an additive genetic model to assess for association with disease. This translates to a model where having 0, 1, or 2 alleles of a genetic variant increases the risk of the disease linearly. However, there are situations where those same alleles instead of increasing risk additively increase risk multiplicatively. That is, having 0, 1, or 2 alleles increases risk under one set of conditions (body mass index [BMI]< 25 kg/m2) from 1 to 2 to 4 and another set of conditions (BMI> 35 kg/m2) from 1 to 8 to 16 (Fig. 1A). The condition under which the effects of the same genotype changes is called a modifier. Identifying environmental modifiers of genetic risk can be done by looking for gene environment interactions. It is important to identify modifiers of disease because if the modifier can be changed, the increased genetic risk for development of disease can be preferentially and dramatically mitigated. A recent article by Stender et al.(1) examined the effect of adiposity on the risk of developing NAFLD in individuals that carried genetic variants encoding patatin-like phospholipase domain containing 3 (PNPLA3) p. I148M (isoleucine to methionine at position 148), TM6SF2 (transmembrane 6 superfamily member 2) p. E167K (glutamic acid to lysine at position 167), and GCKR (glucokinase regulator)
登录
查看更多内容
影响因子：
4.5
作者：
Speliotes EK;Yerges-Armstrong LM;Wu J;Hernaez R;Kim LJ;Palmer CD;Gudnason V;Eiriksdottir G;Garcia ME;Launer LJ;Nalls MA;Clark JM;Mitchell BD;Shuldiner AR;Butler JL;Tomas M;Hoffmann U;Hwang SJ;Massaro JM;O'Donnell CJ;Sahani DV;Salomaa V;Schadt EE;Schwartz SM;Siscovick DS;NASH CRN;GIANT Consortium;MAGIC Investigators;Voight BF;Carr JJ;Feitosa MF;Harris TB;Fox CS;Smith AV;Kao WH;Hirschhorn JN;Borecki IB;GOLD Consortium
通讯作者：
GOLD Consortium
影响因子：
4.9
作者：
Romeo, S.;Sentinelli, F.;Baroni, M. G.
通讯作者：
Baroni, M. G.
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.
影响因子：
7.1
作者：
Sevastianova, Ksenia;Kotronen, Anna;Yki-Jarvinen, Hannele
通讯作者：
Yki-Jarvinen, Hannele
影响因子：
3.1
作者：
Krawczyk, Marcin;Jimenez-Agueero, Raul;Banales, Jesus M.
通讯作者：
Banales, Jesus M.