Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics.
Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics.
复制标题
使用组织特异性定量相互作用蛋白质组学对全基因组关联研究中的基因座进行注释。
DOI：
10.1038/nmeth.2997
复制
发表时间：
2014-08
期刊：
影响因子：
48
通讯作者：
Olsen, Jesper V.
中科院分区：
文献类型：
--
作者：
Lundby, Alicia;Rossin, Elizabeth J.;Steffensen, Annette B.;Acha, Moshe Ray;Newton-Cheh, Christopher;Pfeufer, Arne;Lyneh, Stacey N.;Olesen, Soren-Peter;Brunak, Soren;Ellinor, Patrick T.;Jukema, J. Wouter;Trompet, Stella;Ford, Ian;Macfarlane, Peter W.;Krijthe, Bouwe P.;Hofman, Albert;Uitterlinden, Andre G.;Stricker, Bruno H.;Nathoe, Hendrik M.;Spiering, Wilko;Daly, Mark J.;Asselbergs, Ikea W.;van der Harst, Pim;Milan, David J.;de Bakker, Paul I. W.;Lage, Kasper;Olsen, Jesper V.
全基因组关联研究（GWAS）已经发现了数千个与复杂性状相关的基因座，但要精确定位这些基因座中的致病基因并利用微妙的关联信号是一个挑战。我们使用组织特异性定量相互作用蛋白质组学来绘制一个由五个基因组成的网络，这些基因参与了孟德尔遗传病长QT综合征（LQTS）。我们将LQTS网络与来自相应的常见复杂性状（QT间期变异）的GWAS基因座整合，以识别候选基因，这些基因随后在非洲爪蟾卵母细胞和斑马鱼中得到证实。我们使用LQTS蛋白质网络来过滤弱GWAS信号，通过识别与网络中的基因接近的单核苷酸多态性（SNP），该网络得到了强有力的蛋白质组学证据的支持。通过该过滤器的三个SNP在复制基因分型后达到全基因组显著性。总的来说，我们提出了一个一般性的策略，提出候选人在GWAS基因座的功能研究和系统地过滤微妙的关联信号，使用组织特异性定量相互作用蛋白质组学。
Genome-wide association studies (GWAS) have identified thousands of loci associated wtih complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LQTS protein network to filter weak GWAS signals by identifying single nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy to propose candidates in GWAS loci for functional studies and to systematically filter subtle association signals using tissue-specific quantitative interaction proteomics.
登录
查看更多内容
影响因子：
30.8
作者：
Arking, Dan E.;Pulit, Sara L.;Crotti, Lia;Van der Harst, Pim;Munroe, Patricia B.;Koopmann, Tamara T.;Sotoodehnia, Nona;Rossin, Elizabeth J.;Morley, Michael;Wang, Xinchen;Johnson, Andrew D.;Lundby, Alicia;Gudbjartsson, Daniel F.;Noseworthy, Peter A.;Eijgelsheim, Mark;Bradford, Yuki;Tarasov, Kirill V.;Dorr, Marcus;Miiller-Nurasyid, Martina;Lahtinen, Annukka M.;Nolte, Ilja M.;Smith, Albert Vernon;Bis, Joshua C.;Isaacs, Aaron;Newhouse, Stephen J.;Evans, Daniel S.;Post, Wendy S.;Waggott, Daryl;Lyytikainen, Leo-Pekka;Hicks, Andrew A.;Eisele, Lewin;Ellinghaus, David;Hayward, Caroline;Navarro, Pau;Ulivi, Sheila;Tanaka, Toshiko;Tester, David J.;Chatel, Stephanie;Gustafsson, Stefan;Kumari, Meena;Morris, Richard W.;Naluai, Asa T.;Padmanabhan, Sandosh;Kluttig, Alexander;Strohmer, Bernhard;Panayiotou, Andrie G.;Torres, Maria;Knoflach, Michael;Hubacek, Jaroslav A.;Slowikowski, Kamil;Raychaudhuri, Soumya;Kumar, Runjun D.;Harris, Tamara B.;Launer, Lenore J.;Shuldiner, Alan R.;Alonso, Alvaro;Bader, Joel S.;EhreT, Georg;Huang, Hailiang;Kao, W. H. Linda;Strait, James B.;Macfarlane, Peter W.;Brown, Morris;Caulfield, Mark J.;Samani, Nilesh J.;Kronenberg, Florian;Willeit, Johann;Smith, J. Gustav;Greiser, Karin H.;Schwabedissen, Henriette Meyer Zu;Werdan, Karl;Carella, Massimo;Zelante, Leopoldo;Heckbert, Susan R.;Psaty, Bruce M.;Rotter, Jerome I.;Kolcic, Ivana;Poagek, Ozren;Wright, Alan F.;Griffin, Maura;Daly, Mark J.;Arnar, David O.;Holm, Hilma;Thorsteinsdottir, Unnur;Denny, Joshua C.;Roden, Dan M.;Zuvich, Rebecca L.;Emilsson, Valur;Plump, Andrew S.;Larson, Martin G.;O'Donnell, Christopher J.;Yin, Xiaoyan;Bobboll, Marco;D'Adamo, Adamo P.;Iorio, Annamaria;Sinagra, Gianfranco;Carracedo, Angel;Cummings, Steven R.;Nalls, Michael A.;Jula, Antti;Kontula, Kimmo K.;Marjamaa, Annukka;Oikarinen, Lasse;Perola, Markus;Porthan, Kimmo;Erbe, Raimund;Hoffmann, Per;Jockel, Karl-Heinz;Kalsch, Hagen;Nothen, Markus M.;Den Hoed, Marcel;Loos, Ruth J. F.;Thelle, Dag S.;Gieger, Christian;Meitinger, Thomas;Perz, Siegfried;Peters, Annette;Pruchal, Hanna;Sinner, Moritz F.;Waldenberger, Melanie;De Boer, Rudolf A.;Franke, Lude;Van der Vleuten, Pieter A.;Beckmann, Britt Maria;Martens, Eimo;Bardail, Abdennasser;Hofman, Nynke;Wilde, Arthur A. M.;Behr, Elijah R.;Dalageorgou, Chrysoula;Giudicessi, John R.;Medeiros-Domingo, Argelia;Barc, Julien;Kyndt, Florence;Probst, Vincent;Ghidoni, Alice;Insolia, Roberto;Hamilton, Robert M.;Scherer, Stephen W.;Brandimarto, Jeffrey;Margulies, Kenneth;Moravec, Christine E.;Del Greco, Fabiola;Fuchsberger, Christian;O'Connell, Jeffrey R.;Lee, Wai K.;Watt, Graham C. M.;Campbell, Harry;Wild, Sarah H.;El Mokhtari, Nour E.;Frey, Norbert;Asselbergs, Folkert W.;Leach, Irene Mateo;Navis, Gerjan;Van den Berg, Maarten P.;Van Veldhuisen, Dirk J.;Kellis, Manolis;Krijthe, Bouwe P.;Franco, Oscar H.;Hofman, Albert;Kors, Jan A.;Uitterlinden, Andre G.;Witteman, Jacqueline C. M.;Kedenko, Lyudmyla;Lamina, Claudia;Oostra, Ben A.;Abecasis, Goncalo R.;Lakatta, Edward G.;Mulas, Antonella;Orru, Marco;Schlessinger, David;Uda, Manuela;Markus, Marcello R. P.;Volker, Uwe;Snieder, Harold;Spector, Timothy D.;Arnlov, Johan;Lind, Lars;Sundstrom, Johan;Syvanen, Ann-Christine;Kivimaki, Mika;Kahonen, Mika;Mononen, Nina;Raitakari, I. T.;Viikari, Jorma S.;Adamkova, Vera;Kiech, Stefan;Brion, Maria;Nicolaides, Andrew N.;Paulweber, Bernhard;Haerting, Johannes;Dominiczak, Anna F.;Nyberg, Fredrik;Whincup, Peter H.;Hingorani, Aroon D.;Schott, Jean-Jacques;Bezzina, Connie R.;Ingelsson, Erik;Ferrucci, Luigi;Gaspariniin, Paolo;Wilson, James F.;Rudan, Igor;Franke, Andre;Miihleisen, Thomas W.;Pramstaller, Peter P.;Lehtimaki, Terho J.;Paterson, Andrew D.;Parsa, Afshin;Liu, Yongmei;Van Duijn, Cornelia M.;Siscovick, David S.;Gudnason, Vilmundur;Jamshidi, Yalda;Salomaa, Veikko;Felix, Stephan B.;Sanna, Serena;Ritchie, Marylyn D.;Stricker, Bruno H.;Stefansson, Karl;Boyer, Laurie A.;Cappola, Thomas P.;Olsen, Jesper V.;Lage, Kasper;Schwartz, Peter J.;Kaab, Stefan;Chakravarti, Aravinda;Ackerman, Michael J.;Pfeufer, Arne;De Bakker, Paul I. W.;Newton-Cheh, Christopher
通讯作者：
Newton-Cheh, Christopher
DOI：
10.1007/978-1-61779-148-2_10
发表时间：
2011-01-01
期刊：
GEL-FREE PROTEOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Lundby, Alicia;Olsen, Jesper V.
通讯作者：
Olsen, Jesper V.
影响因子：
30.8
作者：
Wang, Q;Curran, ME;Keating, MT
通讯作者：
Keating, MT
影响因子：
30.8
作者：
Pfeufer, Arne;Sanna, Serena;Arking, Dan E.;Mueller, Martina;Gateva, Vesela;Fuchsberger, Christian;Ehret, Georg B.;Orru, Marco;Pattaro, Cristian;Koettgen, Anna;Perz, Siegfried;Usala, Gianluca;Barbalic, Maja;Li, Man;Puetz, Benno;Scuteri, Angelo;Prineas, Ronald J.;Sinner, Moritz F.;Gieger, Christian;Najjar, Samer S.;Kao, W. H. Linda;Muehleisen, Thomas W.;Dei, Mariano;Happle, Christine;Moehlenkamp, Stefan;Crisponi, Laura;Erbel, Raimund;Joeckel, Karl-Heinz;Naitza, Silvia;Steinbeck, Gerhard;Marroni, Fabio;Hicks, Andrew A.;Lakatta, Edward;Mueller-Myhsok, Bertram;Pramstaller, Peter P.;Wichmann, H-Erich;Schlessinger, David;Boerwinkle, Eric;Meitinger, Thomas;Uda, Manuela;Coresh, Josef;Kaeaeb, Stefan;Abecasis, Goncalo R.;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
37.8
作者：
Vatta, Matteo;Ackerman, Michael J.;Towbin, Jeffrey A.
通讯作者：
Towbin, Jeffrey A.