Beyond GWASs: illuminating the dark road from association to function.
作者： Stacey L. Edwards , Jonathan Beesley , Juliet D. French , Alison M. Dunning
DOI: 10.1016/J.AJHG.2013.10.012
关键词: Gene 、 Genetics 、 Epigenetics 、 Non-coding RNA 、 Genetic association 、 Genetic variation 、 Epigenesis 、 Biology 、 Computational biology 、 Genome 、 Genome-wide association study
摘要: Genome-wide association studies (GWASs) have enabled the discovery of common genetic variation contributing to normal and pathological traits clinical drug responses, but recognizing precise targets these associations is now major challenge. Here, we review recent approaches functional follow-up GWAS loci, including fine mapping signal(s), prioritization putative SNPs by integration epidemiological bioinformatic methods, in vitro in vivo experimental verification predicted molecular mechanisms for identifying targeted genes. The majority GWAS-identified variants fall in noncoding regions genome. Therefore, this focuses on strategies assessing likely affected variants; such include transcriptional regulation, RNA function, epigenetic regulation. These already accelerated progress from biological knowledge might ultimately guide development prognostic, preventive, therapeutic measures.
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Rebecca Hein, Melanie Maranian, John L Hopper, Miroslaw K Kapuscinski, Melissa C Southey, Daniel J Park, Marjanka K Schmidt, Annegien Broeks, Frans BL Hogervorst, H Bas Bueno-de-Mesquit, Kenneth R Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guenel, Emilie Cordina-Duverger, Florence Menegaux, Therese Truong, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Roger L Milne, Jose Ignacio Arias Perez, M Pilar Zamora, Javier Benitez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A Clarke, Hermann Brenner, Heiko Mueller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R Bartram, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, GENICA Network, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V Bogdanova, Iosif V Zalutsky, Natalia N Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, kConFab Investigators, AOCS Group, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J Couch, Janet E Olson, Xianshu Wang, Zachary Fredericksen, Graham G Giles, Laura Baglietto, Catriona A McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børresen-Dale, Esther M John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Jonine D Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E Sherman, Maartje Hooning, John WM Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W Brock, Simon S Cross, Malcolm WR Reed, Shahana Ahmed, Maya Ghoussaini, Paul DP Pharoah, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, None, Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) PLoS ONE. ,vol. 7, pp. e42380- ,(2012) , 10.1371/JOURNAL.PONE.0042380
Megan P Hitchins, Robert W Rapkins, Chau-To Kwok, Sameer Srivastava, Justin JL Wong, Levon M Khachigian, Patsie Polly, Jack Goldblatt, Robyn L Ward, Dominantly Inherited Constitutional Epigenetic Silencing of MLH1 in a Cancer-Affected Family Is Linked to a Single Nucleotide Variant within the 5'UTR Cancer Cell. ,vol. 20, pp. 200- 213 ,(2011) , 10.1016/J.CCR.2011.07.003
B. D. Galvin, K. C. Hart, A. N. Meyer, M. K. Webster, D. J. Donoghue, Constitutive receptor activation by Crouzon syndrome mutations in fibroblast growth factor receptor (FGFR)2 and FGFR2/Neu chimeras Proceedings of the National Academy of Sciences of the United States of America. ,vol. 93, pp. 7894- 7899 ,(1996) , 10.1073/PNAS.93.15.7894
Alexandra C. Nica, Leopold Parts, Daniel Glass, James Nisbet, Amy Barrett, Magdalena Sekowska, Mary Travers, Simon Potter, Elin Grundberg, Kerrin Small, Åsa K. Hedman, Veronique Bataille, Jordana Tzenova Bell, Gabriela Surdulescu, Antigone S. Dimas, Catherine Ingle, Frank O. Nestle, Paola di Meglio, Josine L. Min, Alicja Wilk, Christopher J. Hammond, Neelam Hassanali, Tsun-Po Yang, Stephen B. Montgomery, Steve O'Rahilly, Cecilia M. Lindgren, Krina T. Zondervan, Nicole Soranzo, Inês Barroso, Richard Durbin, Kourosh Ahmadi, Panos Deloukas, Mark I. McCarthy, Emmanouil T. Dermitzakis, Timothy D. Spector, , The architecture of gene regulatory variation across multiple human tissues: the MuTHER study PLOS Genetics. ,vol. 7, ,(2011) , 10.1371/JOURNAL.PGEN.1002003
Chaochun Liu, Bibekanand Mallick, Dang Long, William A Rennie, Adam Wolenc, C Steven Carmack, Ye Ding, None, CLIP-based prediction of mammalian microRNA binding sites Nucleic Acids Research. ,vol. 41, ,(2013) , 10.1093/NAR/GKT435
Gosia Trynka, , Karen A Hunt, Nicholas A Bockett, Jihane Romanos, Vanisha Mistry, Agata Szperl, Sjoerd F Bakker, Maria Teresa Bardella, Leena Bhaw-Rosun, Gemma Castillejo, Emilio G de la Concha, Rodrigo Coutinho de Almeida, Kerith-Rae M Dias, Cleo C van Diemen, Patrick C A Dubois, Richard H Duerr, Sarah Edkins, Lude Franke, Karin Fransen, Javier Gutierrez, Graham A R Heap, Barbara Hrdlickova, Sarah Hunt, Leticia Plaza Izurieta, Valentina Izzo, Leo A B Joosten, Cordelia Langford, Maria Cristina Mazzilli, Charles A Mein, Vandana Midah, Mitja Mitrovic, Barbara Mora, Marinita Morelli, Sarah Nutland, Concepción Núñez, Suna Onengut-Gumuscu, Kerra Pearce, Mathieu Platteel, Isabel Polanco, Simon Potter, Carmen Ribes-Koninckx, Isis Ricaño-Ponce, Stephen S Rich, Anna Rybak, José Luis Santiago, Sabyasachi Senapati, Ajit Sood, Hania Szajewska, Riccardo Troncone, Jezabel Varadé, Chris Wallace, Victorien M Wolters, Alexandra Zhernakova, B K Thelma, Bozena Cukrowska, Elena Urcelay, Jose Ramon Bilbao, M Luisa Mearin, Donatella Barisani, Jeffrey C Barrett, Vincent Plagnol, Panos Deloukas, Cisca Wijmenga, David A van Heel, , , Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease Nature Genetics. ,vol. 43, pp. 1193- 1201 ,(2011) , 10.1038/NG.998
Amartya Sanyal, Bryan R. Lajoie, Gaurav Jain, Job Dekker, The long-range interaction landscape of gene promoters Nature. ,vol. 489, pp. 109- 113 ,(2012) , 10.1038/NATURE11279
Ian Tomlinson, Kimmo Palin, Esko Ukkonen, Auli Karhu, Jussi Taipale, Lauri A Aaltonen, Sari Tuupanen, Mikko Turunen, Rainer Lehtonen, Outi Hallikas, Sakari Vanharanta, Teemu Kivioja, Mikael Björklund, Gonghong Wei, Jian Yan, Iina Niittymäki, Jukka-Pekka Mecklin, Heikki Järvinen, Ari Ristimäki, Mariachiara Di-Bernardo, Phil East, Luis Carvajal-Carmona, Richard S Houlston, The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling Nature Genetics. ,vol. 41, pp. 885- 890 ,(2009) , 10.1038/NG.406
Teri A Manolio, Francis S Collins, Nancy J Cox, David B Goldstein, Lucia A Hindorff, David J Hunter, Mark I McCarthy, Erin M Ramos, Lon R Cardon, Aravinda Chakravarti, Judy H Cho, Alan E Guttmacher, Augustine Kong, Leonid Kruglyak, Elaine Mardis, Charles N Rotimi, Montgomery Slatkin, David Valle, Alice S Whittemore, Michael Boehnke, Andrew G Clark, Evan E Eichler, Greg Gibson, Jonathan L Haines, Trudy FC Mackay, Steven A McCarroll, Peter M Visscher, None, Finding the missing heritability of complex diseases. Nature. ,vol. 461, pp. 747- 753 ,(2009) , 10.1038/NATURE08494
Nasim Ahmadiyeh, Mark M Pomerantz, Chiara Grisanzio, Paula Herman, Li Jia, Vanessa Almendro, Housheng Hansen He, Myles Brown, X Shirley Liu, Matt Davis, Jennifer L Caswell, Christine A Beckwith, Adam Hills, Laura MacConaill, Gerhard A Coetzee, Meredith M Regan, Matthew L Freedman, None, 8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 9742- 9746 ,(2010) , 10.1073/PNAS.0910668107