Analysis of the joint effect of SNPs to identify independent loci and allelic heterogeneity in schizophrenia GWAS data.
Analysis of the joint effect of SNPs to identify independent loci and allelic heterogeneity in schizophrenia GWAS data.
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DOI：
10.1038/s41398-017-0033-2
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发表时间：
2017-12-18
影响因子：
6.8
通讯作者：
Le Hellard S
中科院分区：
文献类型：
--
作者：
Polushina T;Giddaluru S;Bettella F;Espeseth T;Lundervold AJ;Djurovic S;Cichon S;Hoffmann P;Nöthen MM;Steen VM;Andreassen OA;Le Hellard S
我们已经测试了已发表的方法，用于捕获等位基因异质性和识别联合效应位点，以揭示更多的精神分裂症（SCZ）的“隐藏遗传性”。我们使用了两种工具，cojo-GCTA和multi-SNP，来分析精神病基因组学联盟（PGC）关于SCZ的最新全基因组关联研究（GWAS）的元统计数据。cojo-GCTA中p值<10−7的标记物的逐步回归识别出96个独立信号。85个通过了全基因组显著性阈值。CLUMP对cojo-GCTA的交叉验证率为76%，即，通过Cojo-GCTA发现，使用CLUMP由PGC鉴定的26个位点依赖于另一个位点。cojo-GCTA和多SNP之间的重叠更好（高达92%）。在联合效应模型中，三个标记达到全基因组显著性（5 × 10−8）。此外，两个位点显示可能的等位基因异质性内1 Mb的基因组区域，而CLUMP分析已确定16个这样的区域。Cojo-GCTA比CLUMP识别更少的独立位点，并且似乎更保守，可能是因为它考虑了标记之间的长距离LD和相互作用效应。这些发现也解释了为什么在cojo-GCTA分析后，具有可能等位基因异质性的较少位点仍然显著。使用多SNP，在阈值10−7处选择了86个标记。多SNP识别较少的独立信号，由于数据的分裂和使用较小的样本。我们建议使用cojo-GCTA和multi-SNP对所有性状进行GWAS后分析，以调用独立位点。我们的结论是，只有少数位点在SCZ显示联合效应或等位基因异质性，但这可能是由于缺乏权力的数据集。
We have tested published methods for capturing allelic heterogeneity and identifying loci of joint effects to uncover more of the “hidden heritability” of schizophrenia (SCZ). We used two tools, cojo-GCTA and multi-SNP, to analyze meta-statistics from the latest genome-wide association study (GWAS) on SCZ by the Psychiatric Genomics Consortium (PGC). Stepwise regression on markers with p values <10−7 in cojo-GCTA identified 96 independent signals. Eighty-five passed the genome-wide significance threshold. Cross-validation of cojo-GCTA by CLUMP was 76%, i.e., 26 of the loci identified by the PGC using CLUMP were found to be dependent on another locus by cojo-GCTA. The overlap between cojo-GCTA and multi-SNP was better (up to 92%). Three markers reached genome-wide significance (5 × 10−8) in a joint effect model. In addition, two loci showed possible allelic heterogeneity within 1-Mb genomic regions, while CLUMP analysis had identified 16 such regions. Cojo-GCTA identified fewer independent loci than CLUMP and seems to be more conservative, probably because it accounts for long-range LD and interaction effects between markers. These findings also explain why fewer loci with possible allelic heterogeneity remained significant after cojo-GCTA analysis. With multi-SNP, 86 markers were selected at the threshold 10−7. Multi-SNP identifies fewer independent signals, due to splitting of the data and use of smaller samples. We recommend that cojo-GCTA and multi-SNP are used for post-GWAS analysis of all traits to call independent loci. We conclude that only a few loci in SCZ show joint effects or allelic heterogeneity, but this could be due to lack of power for that data set.
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影响因子：
4.8
作者：
Athanasiu L;Mattingsdal M;Kähler AK;Brown A;Gustafsson O;Agartz I;Giegling I;Muglia P;Cichon S;Rietschel M;Pietiläinen OP;Peltonen L;Bramon E;Collier D;Clair DS;Sigurdsson E;Petursson H;Rujescu D;Melle I;Steen VM;Djurovic S;Andreassen OA
通讯作者：
Andreassen OA
影响因子：
64.8
作者：
Ripke, Stephan;Neale, Benjamin M.;Corvin, Aiden;Walters, James T. R.;Farh, Kai-How;Holmans, Peter A.;Lee, Phil;Bulik-Sullivan, Brendan;Collier, David A.;Huang, Hailiang;Pers, Tune H.;Agartz, Ingrid;Agerbo, Esben;Albus, Margot;Alexander, Madeline;Amin, Farooq;Bacanu, Silviu A.;Begemann, Martin;Belliveau, Richard A., Jr.;Bene, Judit;Bergen, Sarah E.;Bevilacqua, Elizabeth;Bigdeli, Tim B.;Black, Donald W.;Bruggeman, Richard;Buccola, Nancy G.;Buckner, Randy L.;Byerley, William;Cahn, Wiepke;Cai, Guiqing;Campion, Dominique;Cantor, Rita M.;Carr, Vaughan J.;Carrera, Noa;Catts, Stanley V.;Chambert, Kimberly D.;Chan, Raymond C. K.;Chen, Ronald Y. L.;Chen, Eric Y. H.;Cheng, Wei;Cheung, Eric F. C.;Chong, Siow Ann;Cloninger, C. Robert;Cohen, David;Cohen, Nadine;Cormican, Paul;Craddock, Nick;Crowley, James J.;Curtis, David;Davidson, Michael;Davis, Kenneth L.;Degenhardt, Franziska;Del Favero, Jurgen;Demontis, Ditte;Dikeos, Dimitris;Dinan, Timothy;Djurovic, Srdjan;Donohoe, Gary;Drapeau, Elodie;Duan, Jubao;Dudbridge, Frank;Durmishi, Naser;Eichhammer, Peter;Eriksson, Johan;Escott-Price, Valentina;Essioux, Laurent;Fanous, Ayman H.;Farrell, Martilias S.;Frank, Josef;Franke, Lude;Freedman, Robert;Freimer, Nelson B.;Friedl, Marion;Friedman, Joseph I.;Fromer, Menachem;Genovese, Giulio;Georgieva, Lyudmila;Giegling, Ina;Giusti-Rodriguez, Paola;Godard, Stephanie;Goldstein, Jacqueline I.;Golimbet, Vera;Gopal, Srihari;Gratten, Jacob;de Haan, Lieuwe;Hammer, Christian;Hamshere, Marian L.;Hansen, Mark;Hansen, Thomas;Haroutunian, Vahram;Hartmann, Annette M.;Henskens, Frans A.;Herms, Stefan;Hirschhorn, Joel N.;Hoffmann, Per;Hofman, Andrea;Hollegaard, Mads V.;Hougaard, David M.;Ikeda, Masashi;Joa, Inge;Julia, Antonio;Kahn, Rene S.;Kalaydjieva, Luba;Karachanak-Yankova, Sena;Karjalainen, Juha;Kavanagh, David;Keller, Matthew C.;Kennedy, James L.;Khrunin, Andrey;Kim, Yunjung;Klovins, Janis;Knowles, James A.;Konte, Bettina;Kucinskas, Vaidutis;Kucinskiene, Zita Ausrele;Kuzelova-Ptackova, Hana;Kahler, Anna K.;Laurent, Claudine;Keong, Jimmy Lee Chee;Lee, S. Hong;Legge, Sophie E.;Lerer, Bernard;Li, Miaoxin;Li, Tao;Liang, Kung-Yee;Lieberman, Jeffrey;Limborska, Svetlana;Loughland, Carmel M.;Lubinski, Jan;Lonnqvist, Jouko;Macek, Milan, Jr.;Magnusson, Patrik K. E.;Maher, Brion S.;Maier, Wolfgang;Mallet, Jacques;Marsal, Sara;Mattheisen, Manuel;Mattingsdal, Morten;McCarley, Robert W.;McDonald, Colm;McIntosh, Andrew M.;Meier, Sandra;Meijer, Carin J.;Melegh, Bela;Melle, Ingrid;Mesholam-Gately, Raquelle I.;Metspalu, Andres;Michie, Patricia T.;Milani, Lili;Milanova, Vihra;Mokrab, Younes;Morris, Derek W.;Mors, Ole;Murphy, Kieran C.;Murray, Robin M.;Myin-Germeys, Inez;Mueller-Myhsok, Bertram;Nelis, Mari;Nenadic, Igor;Nertney, Deborah A.;Nestadt, Gerald;Nicodemus, Kristin K.;Nikitina-Zake, Liene;Nisenbaum, Laura;Nordin, Annelie;O'Callaghan, Eadbhard;O'Dushlaine, Colm;O'Neill, F. Anthony;Oh, Sang-Yun;Olincy, Ann;Olsen, Line;Van Os, Jim;Pantelis, Christos;Papadimitriou, George N.;Papiol, Sergi;Parkhomenko, Elena;Pato, Michele T.;Paunio, Tiina;Pejovic-Milovancevic, Milica;Perkins, Diana O.;Pietilainen, Olli;Pimm, Jonathan;Pocklington, Andrew J.;Powell, John;Price, Alkes;Pulver, Ann E.;Purcell, Shaun M.;Quested, Digby;Rasmussen, Henrik B.;Reichenberg, Abraham;Reimers, Mark A.;Richards, Alexander L.;Roffman, Joshua L.;Roussos, Panos;Ruderfer, Douglas M.;Salomaa, Veikko;Sanders, Alan R.;Schall, Ulrich;Schubert, Christian R.;Schulze, Thomas G.;Schwab, Sibylle G.;Scolnick, Edward M.;Scott, Rodney J.;Seidman, Larry J.;Shi, Jianxin;Sigurdsson, Engilbert;Silagadze, Teimuraz;Silverman, Jeremy M.;Sim, Kang;Slominsky, Petr;Smoller, Jordan W.;So, Hon-Cheong;Spencer, Chris C. A.;Stahl, Eli A.;Stefansson, Hreinn;Steinberg, Stacy;Stogmann, Elisabeth;Straub, Richard E.;Strengman, Eric;Strohmaier, Jana;Stroup, T. Scott;Subramaniam, Mythily;Suvisaari, Jaana;Svrakic, Dragan M.;Szatkiewicz, Jin P.;Soderman, Erik;Thirumalai, Srinivas;Toncheva, Draga;Tosato, Sarah;Veijola, Juha;Waddington, John;Walsh, Dermot;Wang, Dai;Wang, Qiang;Webb, Bradley T.;Weiser, Mark;Wildenauer, Dieter B.;Williams, Nigel M.;Williams, Stephanie;Witt, Stephanie H.;Wolen, Aaron R.;Wong, Emily H. M.;Wormley, Brandon K.;Xi, Hualin Simon;Zai, Clement C.;Zheng, Xuebin;Zimprich, Fritz;Wray, Naomi R.;Stefansson, Kari;Visscher, Peter M.;Adolfsson, Rolf;Andreassen, Ole A.;Blackwood, Douglas H. R.;Bramon, Elvira;Buxbaum, Joseph D.;Borglum, Anders D.;Cichon, Sven;Darvasi, Ariel;Domenici, Enrico;Ehrenreich, Hannelore;Esko, Tonu;Gejman, Pablo V.;Gill, Michael;Gurling, Hugh;Hultman, Christina M.;Iwata, Nakao;Jablensky, Assen V.;Jonsson, Erik G.;Kendler, Kenneth S.;Kirov, George;Knight, Jo;Lencz, Todd;Levinson, Douglas F.;Li, Qingqin S.;Liu, Jianjun;Malhotra, Anil K.;McCarroll, Steven A.;McQuillin, Andrew;Moran, Jennifer L.;Mortensen, Preben B.;Mowry, Bryan J.;Noethen, Markus M.;Ophoff, Roel A.;Owen, Michael J.;Palotie, Aarno;Pato, Carlos N.;Petryshen, Tracey L.;Posthuma, Danielle;Rietschel, Marcella;Riley, Brien P.;Rujescu, Dan;Sham, Pak C.;Sklar, Pamela;St Clair, David;Weinberger, Daniel R.;Wendland, Jens R.;Werge, Thomas;Daly, Mark J.;Sullivan, Patrick F.;O'Donovan, Michael C.
通讯作者：
O'Donovan, Michael C.
影响因子：
4
作者：
Weissglas-Volkov D;Aguilar-Salinas CA;Nikkola E;Deere KA;Cruz-Bautista I;Arellano-Campos O;Muñoz-Hernandez LL;Gomez-Munguia L;Ordoñez-Sánchez ML;Reddy PM;Lusis AJ;Matikainen N;Taskinen MR;Riba L;Cantor RM;Sinsheimer JS;Tusie-Luna T;Pajukanta P
通讯作者：
Pajukanta P
DOI：
10.1093/bioinformatics/btq340
发表时间：
2010-09-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Willer CJ;Li Y;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
64.8
作者：
Okbay A;Beauchamp JP;Fontana MA;Lee JJ;Pers TH;Rietveld CA;Turley P;Chen GB;Emilsson V;Meddens SF;Oskarsson S;Pickrell JK;Thom K;Timshel P;de Vlaming R;Abdellaoui A;Ahluwalia TS;Bacelis J;Baumbach C;Bjornsdottir G;Brandsma JH;Pina Concas M;Derringer J;Furlotte NA;Galesloot TE;Girotto G;Gupta R;Hall LM;Harris SE;Hofer E;Horikoshi M;Huffman JE;Kaasik K;Kalafati IP;Karlsson R;Kong A;Lahti J;van der Lee SJ;deLeeuw C;Lind PA;Lindgren KO;Liu T;Mangino M;Marten J;Mihailov E;Miller MB;van der Most PJ;Oldmeadow C;Payton A;Pervjakova N;Peyrot WJ;Qian Y;Raitakari O;Rueedi R;Salvi E;Schmidt B;Schraut KE;Shi J;Smith AV;Poot RA;St Pourcain B;Teumer A;Thorleifsson G;Verweij N;Vuckovic D;Wellmann J;Westra HJ;Yang J;Zhao W;Zhu Z;Alizadeh BZ;Amin N;Bakshi A;Baumeister SE;Biino G;Bønnelykke K;Boyle PA;Campbell H;Cappuccio FP;Davies G;De Neve JE;Deloukas P;Demuth I;Ding J;Eibich P;Eisele L;Eklund N;Evans DM;Faul JD;Feitosa MF;Forstner AJ;Gandin I;Gunnarsson B;Halldórsson BV;Harris TB;Heath AC;Hocking LJ;Holliday EG;Homuth G;Horan MA;Hottenga JJ;de Jager PL;Joshi PK;Jugessur A;Kaakinen MA;Kähönen M;Kanoni S;Keltigangas-Järvinen L;Kiemeney LA;Kolcic I;Koskinen S;Kraja AT;Kroh M;Kutalik Z;Latvala A;Launer LJ;Lebreton MP;Levinson DF;Lichtenstein P;Lichtner P;Liewald DC;LifeLines Cohort Study;Loukola A;Madden PA;Mägi R;Mäki-Opas T;Marioni RE;Marques-Vidal P;Meddens GA;McMahon G;Meisinger C;Meitinger T;Milaneschi Y;Milani L;Montgomery GW;Myhre R;Nelson CP;Nyholt DR;Ollier WE;Palotie A;Paternoster L;Pedersen NL;Petrovic KE;Porteous DJ;Räikkönen K;Ring SM;Robino A;Rostapshova O;Rudan I;Rustichini A;Salomaa V;Sanders AR;Sarin AP;Schmidt H;Scott RJ;Smith BH;Smith JA;Staessen JA;Steinhagen-Thiessen E;Strauch K;Terracciano A;Tobin MD;Ulivi S;Vaccargiu S;Quaye L;van Rooij FJ;Venturini C;Vinkhuyzen AA;Völker U;Völzke H;Vonk JM;Vozzi D;Waage J;Ware EB;Willemsen G;Attia JR;Bennett DA;Berger K;Bertram L;Bisgaard H;Boomsma DI;Borecki IB;Bültmann U;Chabris CF;Cucca F;Cusi D;Deary IJ;Dedoussis GV;van Duijn CM;Eriksson JG;Franke B;Franke L;Gasparini P;Gejman PV;Gieger C;Grabe HJ;Gratten J;Groenen PJ;Gudnason V;van der Harst P;Hayward C;Hinds DA;Hoffmann W;Hyppönen E;Iacono WG;Jacobsson B;Järvelin MR;Jöckel KH;Kaprio J;Kardia SL;Lehtimäki T;Lehrer SF;Magnusson PK;Martin NG;McGue M;Metspalu A;Pendleton N;Penninx BW;Perola M;Pirastu N;Pirastu M;Polasek O;Posthuma D;Power C;Province MA;Samani NJ;Schlessinger D;Schmidt R;Sørensen TI;Spector TD;Stefansson K;Thorsteinsdottir U;Thurik AR;Timpson NJ;Tiemeier H;Tung JY;Uitterlinden AG;Vitart V;Vollenweider P;Weir DR;Wilson JF;Wright AF;Conley DC;Krueger RF;Davey Smith G;Hofman A;Laibson DI;Medland SE;Meyer MN;Yang J;Johannesson M;Visscher PM;Esko T;Koellinger PD;Cesarini D;Benjamin DJ
通讯作者：
Benjamin DJ