Bayesian refinement of association signals for 14 loci in 3 common diseases.
Bayesian refinement of association signals for 14 loci in 3 common diseases.
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DOI：
10.1038/ng.2435
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发表时间：
2012-12
期刊：
影响因子：
30.8
通讯作者：
Donnelly, Peter
中科院分区：
文献类型：
--
作者：
Maller, Julian B.;McVean, Gilean;Byrnes, Jake;Vukcevic, Damjan;Palin, Kimmo;Su, Zhan;Howson, Joanna M. M.;Auton, Adam;Myers, Simon;Morris, Andrew;Pirinen, Matti;Brown, Matthew A.;Burton, Paul R.;Caulfield, Mark J.;Compston, Alastair;Farrall, Martin;Hall, Alistair S.;Hattersley, Andrew T.;Hill, Adrian V. S.;Mathew, Christopher G.;Pembrey, Marcus;Satsangi, Jack;Stratton, Michael R.;Worthington, Jane;Craddock, Nick;Hurles, Matthew;Ouwehand, Willem;Parkes, Miles;Rahman, Nazneen;Duncanson, Audrey;Todd, John A.;Kwiatkowski, Dominic P.;Samani, Nilesh J.;Gough, Stephen C. L.;McCarthy, Mark I.;Deloukas, Panagiotis;Donnelly, Peter
为了进一步研究全基因组关联研究确定的易感基因座，我们对来自对照组和3种疾病的14个相关区域的5500个SNPs进行了基因分型：2型糖尿病(T2D)、冠状动脉疾病(CAD)和Graves病。我们使用贝叶斯定理定义了可信的SNPs集，基于后验概率，这些SNPs集有95%的可能性包含与因果疾病相关的SNPs。在14个区域中，TCF7L2(T2D)、CTLA4(Graves病)和CDKN2A-CDKN2B(T2D)中，大部分后验概率依赖于单个SNP，而在另外4个区域(CDKN2A-CDKN2B(CAD)和CDKAL1、FTO和HEX(T2D))，95%的集合很小，因此排除了大多数SNP的潜在原因。在我们可信的集合中，很少有SNP具有注释功能，这说明了在理解常见疾病易感性的机制方面的局限性。我们的结果还显示了对靶序列进行更详细的映射对于功能研究的价值。
To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves’ disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves’ disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies.
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影响因子：
3.5
作者：
Peden JF;Farrall M
通讯作者：
Farrall M
影响因子：
4.5
作者：
Stranger BE;Montgomery SB;Dimas AS;Parts L;Stegle O;Ingle CE;Sekowska M;Smith GD;Evans D;Gutierrez-Arcelus M;Price A;Raj T;Nisbett J;Nica AC;Beazley C;Durbin R;Deloukas P;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
30.8
作者：
Morris, Andrew P.;Voight, Benjamin F.;Teslovich, Tanya M.;Ferreira, Teresa;Segre, Ayellet V.;Steinthorsdottir, Valgerdur;Strawbridge, Rona J.;Khan, Hassan;Grallert, Harald;Mahajan, Anubha;Prokopenko, Inga;Kang, Hyun Min;Dina, Christian;Esko, Tonu;Fraser, Ross M.;Kanoni, Stavroula;Kumar, Ashish;Lagou, Vasiliki;Langenberg, Claudia;Luan, Jian'an;Lindgren, Cecilia M.;Mueller-Nurasyid, Martina;Pechlivanis, Sonali;Rayner, N. William;Scott, Laura J.;Wiltshire, Steven;Yengo, Loic;Kinnunen, Leena;Rossin, Elizabeth J.;Raychaudhuri, Soumya;Johnson, Andrew D.;Dimas, Antigone S.;Loos, Ruth J. F.;Vedantam, Sailaja;Chen, Han;Florez, Jose C.;Fox, Caroline;Liu, Ching-Ti;Rybin, Denis;Couper, David J.;Kao, Wen Hong L.;Li, Man;Cornelis, Marilyn C.;Kraft, Peter;Sun, Qi;van Dam, Rob M.;Stringham, Heather M.;Chines, Peter S.;Fischer, Krista;Fontanillas, Pierre;Holmen, Oddgeir L.;Hunt, Sarah E.;Jackson, Anne U.;Kong, Augustine;Lawrence, Robert;Meyer, Julia;Perry, John R. B.;Platou, Carl G. P.;Potter, Simon;Rehnberg, Emil;Robertson, Neil;Sivapalaratnam, Suthesh;Stancakova, Alena;Stirrups, Kathleen;Thorleifsson, Gudmar;Tikkanen, Emmi;Wood, Andrew R.;Almgren, Peter;Atalay, Mustafa;Benediktsson, Rafn;Bonnycastle, Lori L.;Burtt, Noel;Carey, Jason;Charpentier, Guillaume;Crenshaw, Andrew T.;Doney, Alex S. F.;Dorkhan, Mozhgan;Edkins, Sarah;Emilsson, Valur;Eury, Elodie;Forsen, Tom;Gertow, Karl;Gigante, Bruna;Grant, George B.;Groves, Christopher J.;Guiducci, Candace;Herder, Christian;Hreidarsson, Astradur B.;Hui, Jennie;James, Alan;Jonsson, Anna;Rathmann, Wolfgang;Klopp, Norman;Kravic, Jasmina;Krjutskov, Kaarel;Langford, Cordelia;Leander, Karin;Lindholm, Eero;Lobbens, Stephane;Mannisto, Satu;Mirza, Ghazala;Muehleisen, Thomas W.;Musk, Bill;Parkin, Melissa;Rallidis, Loukianos;Saramies, Jouko;Sennblad, Bengt;Shah, Sonia;Sigurdsson, Gunnar;Silveira, Angela;Steinbach, Gerald;Thorand, Barbara;Trakalo, Joseph;Veglia, Fabrizio;Wennauer, Roman;Winckler, Wendy;Zabaneh, Delilah;Campbell, Harry;van Duijn, Cornelia;Uitterlinden, Andre G.;Hofman, Albert;Sijbrands, Eric;Abecasis, Goncalo R.;Owen, Katharine R.;Zeggini, Eleftheria;Trip, Mieke D.;Forouhi, Nita G.;Syvanen, Ann-Christine;Eriksson, Johan G.;Peltonen, Leena;Noethen, Markus M.;Balkau, Beverley;Palmer, Colin N. A.;Lyssenko, Valeriya;Tuomi, Tiinamaija;Isomaa, Bo;Hunter, David J.;Qi, Lu;Shuldiner, Alan R.;Roden, Michael;Barroso, Ines;Wilsgaard, Tom;Beilby, John;Hovingh, Kees;Price, Jackie F.;Wilson, James F.;Rauramaa, Rainer;Lakka, Timo A.;Lind, Lars;Dedoussis, George;Njolstad, Inger;Pedersen, Nancy L.;Khaw, Kay-Tee;Wareham, Nicholas J.;Keinanen-Kiukaanniemi, Sirkka M.;Saaristo, Timo E.;Korpi-Hyovalti, Eeva;Saltevo, Juha;Laakso, Markku;Kuusisto, Johanna;Metspalu, Andres;Collins, Francis S.;Mohlke, Karen L.;Bergman, Richard N.;Tuomilehto, Jaakko;Boehm, Bernhard O.;Gieger, Christian;Hveem, Kristian;Cauchi, Stephane;Froguel, Philippe;Baldassarre, Damiano;Tremoli, Elena;Humphries, Steve E.;Saleheen, Danish;Danesh, John;Ingelsson, Erik;Ripatti, Samuli;Salomaa, Veikko;Erbel, Raimund;Joeckel, Karl-Heinz;Moebus, Susanne;Peters, Annette;Illig, Thomas;de Faire, Ulf;Hamsten, Anders;Morris, Andrew D.;Donnelly, Peter J.;Frayling, Timothy M.;Hattersley, Andrew T.;Boerwinkle, Eric;Melander, Olle;Kathiresan, Sekar;Nilsson, Peter M.;Deloukas, Panos;Thorsteinsdottir, Unnur;Groop, Leif C.;Stefansson, Kari;Hu, Frank;Pankow, James S.;Dupuis, Josee;Meigs, James B.;Altshuler, David;Boehnke, Michael;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
30.5
作者：
Steinman, Lawrence
通讯作者：
Steinman, Lawrence
影响因子：
64.8
作者：
Burton, Paul R.;Clayton, David G.;Cardon, Lon R.;Craddock, Nick;Deloukas, Panos;Duncanson, Audrey;Kwiatkowski, Dominic P.;McCarthy, Mark I.;Ouwehand, Willem H.;Samani, Nilesh J.;Todd, John A.;Donnelly, Peter;Barrett, Jeffrey C.;Davison, Dan;Easton, Doug;Evans, David;Leung, Hin-Tak;Marchini, Jonathan L.;Morris, Andrew P.;Spencer, Chris C. A.;Tobin, Martin D.;Attwood, Antony P.;Boorman, James P.;Cant, Barbara;Everson, Ursula;Hussey, Judith M.;Jolley, Jennifer D.;Knight, Alexandra S.;Koch, Kerstin;Meech, Elizabeth;Nutland, Sarah;Prowse, Christopher V.;Stevens, Helen E.;Taylor, Niall C.;Walters, Graham R.;Walker, Neil M.;Watkins, Nicholas A.;Winzer, Thilo;Jones, Richard W.;McArdle, Wendy L.;Ring, Susan M.;Strachan, David P.;Pembrey, Marcus;Breen, Gerome;St Clair, David;Caesar, Sian;Gordon-Smith, Katherine;Jones, Lisa;Fraser, Christine;Green, Elain K.;Grozeva, Detelina;Hamshere, Marian L.;Holmans, Peter A.;Jones, Ian R.;Kirov, George;Moskvina, Valentina;Nikolov, Ivan;O'Donovan, Michael C.;Owen, Michael J.;Collier, David A.;Elkin, Amanda;Farmer, Anne;Williamson, Richard;McGuffin, Peter;Young, Allan H.;Ferrier, I. Nicol;Ball, Stephen G.;Balmforth, Anthony J.;Barrett, Jennifer H.;Bishop, D. Timothy;Iles, Mark M.;Maqbool, Azhar;Yudasheve, Nadira;Hall, Alistair S.;Braund, Peter S.;Dixon, Richard J.;Mangino, Massimo;Stevens, Suzanne;Thompson, John R.;Bredin, Francesca;Tremelling, Mark;Parkes, Miles;Drummond, Hazel;Lees, Charles W.;Nimmo, Elaine R.;Satsangi, Jack;Fisher, Sheila A.;Forbes, Alistair;Lewis, Cathryn M.;Onnie, Clive M.;Prescott, Natalie J.;Sanderson, Jeremy;Mathew, Christopher G.;Barbour, Jamie;Mohiuddin, M. Khalid;Todhunter, Catherine E.;Mansfield, John C.;Ahmad, Tariq;Cummings, Fraser R.;Jewell, Derek P.;Webster, John;Brown, Morris J.;Lathrop, G. Mark;Connell, John;Dominiczak, Anna;Marcano, Carolina A. Braga;Burke, Beverley;Dobson, Richard;Gungadoo, Johannie;Lee, Kate L.;Munroe, Patricia B.;Newhouse, Stephen J.;Onipinla, Abiodun;Wallace, Chris;Xue, Mingzhan;Caulfield, Mark;Farrall, Martin;Barton, Anne;Bruce, Ian N.;Donovan, Hannah;Eyre, Steve;Gilbert, Paul D.;Hider, Samantha L.;Hinks, Anne M.;John, Sally L.;Potter, Catherine;Silman, Alan J.;Symmons, Deborah P. M.;Thomson, Wendy;Worthington, Jane;Dunger, David B.;Widmer, Barry;Frayling, Timothy M.;Freathy, Rachel M.;Lango, Hana;Perry, John R. B.;Shields, Beverley M.;Weedon, Michael N.;Hattersley, Andrew T.;Hitman, Graham A.;Walker, Mark;Elliott, Kate S.;Groves, Christopher J.;Lindgren, Cecilia M.;Rayner, Nigel W.;Timpson, Nicholas J.;Zeggini, Eleftheria;Newport, Melanie;Sirugo, Giorgio;Lynons, Emily;Vannberg, Fredrik;Brown, Matthew A.;Franklyn, Jayne A.;Heward, Joanne M.;Simmonds, Matthew J.;Hill, Adrian V. S.;Bradbury, Linda A.;Farrar, Claire;Pointon, Jennifer J.;Wordsmith, Paul;Gough, Stephen C. L.;Seal, Sheila;Stratton, Michael R.;Rahman, Nazneen;Ban, Maria;Goris, An;Sawcer, Stephen J.;Compston, Alistair;Conway, David;Jallow, Muminatou;Bumpstead, Suzannah J.;Chaney, Amy;Downes, Kate;Ghori, Mohammed J. R.;Gwilliam, Rhian;Inouye, Michael;Keniry, Andrew;King, Emma;McGinnis, Ralph;Potter, Simon;Ravindrarajah, Rathi;Whittaker, Pamela;Withers, David;Easton, Doug;Pereira-Gale, Joanne;Hallgrimsdottir, Ingilef B.;Howie, Bryan N.;Su, Zhan;Teo, Yik Ying;Vukcevic, Damjan;Bentley, David;Caulfield, Mark;Mathew, Christopher G.;Worthington, Jane
通讯作者：
Worthington, Jane