All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs.
作者： Andrew J Schork , Wesley K Thompson , Phillip Pham , Ali Torkamani , J Cooper Roddey
DOI: 10.1371/JOURNAL.PGEN.1003449
关键词:
摘要: Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of heritability common complex phenotypes, but methods are lacking reliably identify remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) leverage genic enrichment in GWAS summary statistics data uncover new loci likely replicate independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP combination with nominal p-values estimate True (TDR = 1−FDR) strata determined by different categories. show a consistent pattern polygenic effects specific annotation categories across diverse greatest SNPs tagging regulatory and coding elements, little introns, negative intergenic SNPs. Stratified directly leads increased TDR given p-value, mirrored replication rates this Crohn's disease GWAS, where find hundredfold variation rate Applying well-established sFDR methodology demonstrate utility stratification improving power rejection from 20% height 300% schizophrenia traditional FDR both fixed at 0.05. Our analyses an inherent among important conceptual implications can be leveraged statistical improve discovery loci.
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Bradley Efron, Large-Scale Inference Cambridge University Press. ,(2010) , 10.1017/CBO9780511761362
Radu V. Craiu, Lei Sun, CHOOSING THE LESSER EVIL: TRADE-OFF BETWEEN FALSE DISCOVERY RATE AND NON-DISCOVERY RATE ,(2008)
A. M. Glazier, Finding Genes That Underlie Complex Traits Science. ,vol. 298, pp. 2345- 2349 ,(2002) , 10.1126/SCIENCE.1076641
Ariane Bruder-Nascimento, Carlos H Camargo, Maria F Sugizaki, Terue Sadatsune, Augusto C Montelli, Alessandro L Mondelli, Eduardo Bagagli, None, Species distribution and susceptibility profile of Candida species in a Brazilian public tertiary hospital. BMC Research Notes. ,vol. 3, pp. 1- 5 ,(2010) , 10.1186/1756-0500-3-1
Jo Knight, Michael R. Barnes, Gerome Breen, Michael E. Weale, Using Functional Annotation for the Empirical Determination of Bayes Factors for Genome-Wide Association Study Analysis PLOS ONE. ,vol. 6, ,(2011) , 10.1371/JOURNAL.PONE.0014808
Carl A Anderson, Gabrielle Boucher, Charlie W Lees, Andre Franke, Mauro D'Amato, Kent D Taylor, James C Lee, Philippe Goyette, Marcin Imielinski, Anna Latiano, Caroline Lagacé, Regan Scott, Leila Amininejad, Suzannah Bumpstead, Leonard Baidoo, Robert N Baldassano, Murray Barclay, Theodore M Bayless, Stephan Brand, Carsten Büning, Jean-Frédéric Colombel, Lee A Denson, Martine De Vos, Marla Dubinsky, Cathryn Edwards, David Ellinghaus, Rudolf SN Fehrmann, James AB Floyd, Timothy Florin, Denis Franchimont, Lude Franke, Michel Georges, Jürgen Glas, Nicole L Glazer, Stephen L Guthery, Talin Haritunians, Nicholas K Hayward, Jean-Pierre Hugot, Gilles Jobin, Debby Laukens, Ian Lawrance, Marc Lémann, Arie Levine, Cecile Libioulle, Edouard Louis, Dermot P McGovern, Monica Milla, Grant W Montgomery, Katherine I Morley, Craig Mowat, Aylwin Ng, William Newman, Roel A Ophoff, Laura Papi, Orazio Palmieri, Laurent Peyrin-Biroulet, Julián Panés, Anne Phillips, Natalie J Prescott, Deborah D Proctor, Rebecca Roberts, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Philip Schumm, Frank Seibold, Yashoda Sharma, Lisa A Simms, Mark Seielstad, A Hillary Steinhart, Stephan R Targan, Leonard H Van Den Berg, Morten Vatn, Hein Verspaget, Thomas Walters, Cisca Wijmenga, David C Wilson, Harm-Jan Westra, Ramnik J Xavier, Zhen Z Zhao, Cyriel Y Ponsioen, Vibeke Andersen, Leif Torkvist, Maria Gazouli, Nicholas P Anagnou, Tom H Karlsen, Limas Kupcinskas, Jurgita Sventoraityte, John C Mansfield, Subra Kugathasan, Mark S Silverberg, Jonas Halfvarson, Jerome I Rotter, Christopher G Mathew, Anne M Griffiths, Richard Gearry, Tariq Ahmad, Steven R Brant, Mathias Chamaillard, Jack Satsangi, Judy H Cho, Stefan Schreiber, Mark J Daly, Jeffrey C Barrett, Miles Parkes, Vito Annese, Hakon Hakonarson, Graham Radford-Smith, Richard H Duerr, Séverine Vermeire, Rinse K Weersma, John D Rioux, None, Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature Genetics. ,vol. 43, pp. 246- 252 ,(2011) , 10.1038/NG.764
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
, Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 Nature Genetics. ,vol. 43, pp. 977- 983 ,(2011) , 10.1038/NG.943
Meera Swami, New from NPG: Genome-wide association study identifies five new schizophrenia loci Nature Medicine. ,vol. 17, pp. 1199- 1199 ,(2011) , 10.1038/NM.2523
Thomas M. Keane, Leo Goodstadt, Petr Danecek, Michael A. White, Kim Wong, Binnaz Yalcin, Andreas Heger, Avigail Agam, Guy Slater, Martin Goodson, Nicholas A. Furlotte, Eleazar Eskin, Christoffer Nellåker, Helen Whitley, James Cleak, Deborah Janowitz, Polinka Hernandez-Pliego, Andrew Edwards, T. Grant Belgard, Peter L. Oliver, Rebecca E. McIntyre, Amarjit Bhomra, Jérôme Nicod, Xiangchao Gan, Wei Yuan, Louise van der Weyden, Charles A. Steward, Sendu Bala, Jim Stalker, Richard Mott, Richard Durbin, Ian J. Jackson, Anne Czechanski, José Afonso Guerra-Assunção, Leah Rae Donahue, Laura G. Reinholdt, Bret A. Payseur, Chris P. Ponting, Ewan Birney, Jonathan Flint, David J. Adams, Mouse genomic variation and its effect on phenotypes and gene regulation Nature. ,vol. 477, pp. 289- 294 ,(2011) , 10.1038/NATURE10413