A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.
A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder.
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DOI：
10.1038/mp.2016.259
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发表时间：
2018-03
影响因子：
11
通讯作者：
Iwata N
中科院分区：
文献类型：
--
作者：
Ikeda M;Takahashi A;Kamatani Y;Okahisa Y;Kunugi H;Mori N;Sasaki T;Ohmori T;Okamoto Y;Kawasaki H;Shimodera S;Kato T;Yoneda H;Yoshimura R;Iyo M;Matsuda K;Akiyama M;Ashikawa K;Kashiwase K;Tokunaga K;Kondo K;Saito T;Shimasaki A;Kawase K;Kitajima T;Matsuo K;Itokawa M;Someya T;Inada T;Hashimoto R;Inoue T;Akiyama K;Tanii H;Arai H;Kanba S;Ozaki N;Kusumi I;Yoshikawa T;Kubo M;Iwata N
全基因组关联研究（GWASs）已经确定了双相情感障碍（BD）的几个易感基因座，并表明BD的遗传结构可以用多基因性解释，其中许多变异有助于BD。在目前的GWAS（I/II期）中，包括来自日本人群的2964例BD受试者和61887例对照受试者，我们在11q12.2（rs 28456，P=6.4 × 10−9）检测到一个新的易感基因座，该区域已知含有血脂水平的调控基因（FADS 1/2/3）。随后的I/II期和精神病学GWAS联盟（PGC-BD）的荟萃分析确定了另一个新的BD基因NFIX（Pbest=5.8 × 10−10），并支持了先前与BD易感性有关的三个区域：MAD 1 L1（Pbest=1.9 × 10−9），TRANK 1（Pbest=2.1 × 10−9）和ODZ 4（Pbest=3.3 × 10−9）。采用风险特征评分分析评估了日本和跨欧洲-日本人群中BD的多基因性。我们在BD病例中检测到更高的分数，无论是在（I/II期）还是在人群中（I/II期和PGC-BD）。这些定义如下：（1）II期为发现，I期为靶点，反之亦然（对于“日本国内比较”，Pbest~10−29，R2~2%）;（2）欧洲PGC-BD为发现，日本BD（I/II期）为靶点（对于“跨欧洲-日本比较”，Pbest~10−13，R2~0.27%）。这种“跨群体”效应得到了使用基于每个群体的效应量估计遗传相关性的支持（可靠性估计值约为0.7）。这些结果表明：（1）两个新的和三个以前涉及的基因座与BD显着相关，（2）BD“风险”效应在日本和欧洲人群之间共享。
Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10−9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10−10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10−9), TRANK1 (Pbest=2.1 × 10−9) and ODZ4 (Pbest=3.3 × 10−9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for ‘within Japanese comparisons’, Pbest~10−29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for ‘trans-European-Japanese comparison,’ Pbest~10−13, R2~0.27%). This ‘trans population’ effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD ‘risk’ effect are shared between Japanese and European populations.
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Lee, S. Hong;Ripke, Stephan;Neale, Benjamin M.;Faraone, Stephen V.;Purcell, Shaun M.;Perlis, Roy H.;Mowry, Bryan J.;Thapar, Anita;Goddard, Michael E.;Witte, John S.;Absher, Devin;Agartz, Ingrid;Akil, Huda;Amin, Farooq;Andreassen, Ole A.;Anjorin, Adebayo;Anney, Richard;Anttila, Verneri;Arking, Dan E.;Asherson, Philip;Azevedo, Maria H.;Backlund, Lena;Badner, Judith A.;Bailey, Anthony J.;Banaschewski, Tobias;Barchas, Jack D.;Barnes, Michael R.;Barrett, Thomas B.;Bass, Nicholas;Battaglia, Agatino;Bauer, Michael;Bayes, Monica;Bellivier, Frank;Bergen, Sarah E.;Berrettini, Wade;Betancur, Catalina;Bettecken, Thomas;Biederman, Joseph;Binder, Elisabeth B.;Black, Donald W.;Blackwood, Douglas H. R.;Bloss, Cinnamon S.;Boehnke, Michael;Boomsma, Dorret I.;Breen, Gerome;Breuer, Rene;Bruggeman, Richard;Cormican, Paul;Buccola, Nancy G.;Buitelaar, Jan K.;Bunney, William E.;Buxbaum, Joseph D.;Byerley, William F.;Byrne, Enda M.;Caesar, Sian;Cahn, Wiepke;Cantor, Rita M.;Casas, Miguel;Chakravarti, Aravinda;Chambert, Kimberly;Choudhury, Khalid;Cichon, Sven;Cloninger, C. Robert;Collier, David A.;Cook, Edwin H.;Coon, Hilary;Cormand, Bru;Corvin, Aiden;Coryell, William H.;Craig, David W.;Craig, Ian W.;Crosbie, Jennifer;Cuccaro, Michael L.;Curtis, David;Czamara, Darina;Datta, Susmita;Dawson, Geraldine;Day, Richard;De Geus, Eco J.;Degenhardt, Franziska;Djurovic, Srdjan;Donohoe, Gary J.;Doyle, Alysa E.;Duan, Jubao;Dudbridge, Frank;Duketis, Eftichia;Ebstein, Richard P.;Edenberg, Howard J.;Elia, Josephine;Ennis, Sean;Etain, Bruno;Fanous, Ayman;Farmer, Anne E.;Ferrier, I. Nicol;Flickinger, Matthew;Fombonne, Eric;Foroud, Tatiana;Frank, Josef;Franke, Barbara;Fraser, Christine;Freedman, Robert;Freimer, Nelson B.;Freitag, Christine M.;Friedl, Marion;Frisen, Louise;Gallagher, Louise;Gejman, Pablo V.;Georgieva, Lyudmila;Gershon, Elliot S.;Geschwind, Daniel H.;Giegling, Ina;Gill, Michael;Gordon, Scott D.;Gordon-Smith, Katherine;Green, Elaine K.;Greenwood, Tiffany A.;Grice, Dorothy E.;Gross, Magdalena;Grozeva, Detelina;Guan, Weihua;Gurling, Hugh;De Haan, Lieuwe;Haines, Jonathan L.;Hakonarson, Hakon;Hallmayer, Joachim;Hamilton, Steven P.;Hamshere, Marian L.;Hansen, Thomas F.;Hartmann, Annette M.;Hautzinger, Martin;Heath, Andrew C.;Henders, Anjali K.;Herms, Stefan;Hickie, Ian B.;Hipolito, Maria;Hoefels, Susanne;Holmans, Peter A.;Holsboer, Florian;Hoogendijk, Witte J.;Hottenga, Jouke-Jan;Hultman, Christina M.;Hus, Vanessa;Ingason, Andres;Ising, Marcus;Jamain, Stephane;Jones, Edward G.;Jones, Ian;Jones, Lisa;Tzeng, Jung-Ying;Kaehler, Anna K.;Kahn, Rene S.;Kandaswamy, Radhika;Keller, Matthew C.;Kennedy, James L.;Kenny, Elaine;Kent, Lindsey;Kim, Yunjung;Kirov, George K.;Klauck, Sabine M.;Klei, Lambertus;Knowles, James A.;Kohli, Martin A.;Koller, Daniel L.;Konte, Bettina;Korszun, Ania;Krabbendam, Lydia;Krasucki, Robert;Kuntsi, Jonna;Kwan, Phoenix;Landen, Mikael;Langstrom, Niklas;Lathrop, Mark;Lawrence, Jacob;Lawson, William B.;Leboyer, Marion;Ledbetter, David H.;Lee, Phil H.;Lencz, Todd;Lesch, Klaus-Peter;Levinson, Douglas F.;Lewis, Cathryn M.;Li, Jun;Lichtenstein, Paul;Lieberman, Jeffrey A.;Lin, Dan-Yu;Linszen, Don H.;Liu, Chunyu;Lohoff, Falk W.;Loo, Sandra K.;Lord, Catherine;Lowe, Jennifer K.;Lucae, Susanne;MacIntyre, Donald J.;Madden, Pamela A. F.;Maestrini, Elena;Magnusson, Patrik K. E.;Mahon, Pamela B.;Maier, Wolfgang;Malhotra, Anil K.;Mane, Shrikant M.;Martin, Christa L.;Martin, Nicholas G.;Mattheisen, Manuel;Matthews, Keith;Mattingsdal, Morten;McCarroll, Steven A.;McGhee, Kevin A.;McGough, James J.;McGrath, Patrick J.;McGuffin, Peter;McInnis, Melvin G.;McIntosh, Andrew;McKinney, Rebecca;McLean, Alan W.;McMahon, Francis J.;McMahon, William M.;McQuillin, Andrew;Medeiros, Helena;Medland, Sarah E.;Meier, Sandra;Melle, Ingrid;Meng, Fan;Meyer, Jobst;Middeldorp, Christel M.;Middleton, Lefkos;Milanova, Vihra;Miranda, Ana;Monaco, Anthony P.;Montgomery, Grant W.;Moran, Jennifer L.;Moreno-De-Luca, Daniel;Morken, Gunnar;Morris, Derek W.;Morrow, Eric M.;Moskvina, Valentina;Muglia, Pierandrea;Muehleisen, Thomas W.;Muir, Walter J.;Mueller-Myhsok, Bertram;Murtha, Michael;Myers, Richard M.;Myin-Germeys, Inez;Neale, Michael C.;Nelson, Stan F.;Nievergelt, Caroline M.;Nikolov, Ivan;Nimgaonkar, Vishwajit;Nolen, Willem A.;Noethen, Markus M.;Nurnberger, John I.;Nwulia, Evaristus A.;Nyholt, Dale R.;O'Dushlaine, Colm;Oades, Robert D.;Olincy, Ann;Oliveira, Guiomar;Olsen, Line;Ophoff, Roel A.;Osby, Urban;Owen, Michael J.;Palotie, Aarno;Parr, Jeremy R.;Paterson, Andrew D.;Pato, Carlos N.;Pato, Michele T.;Penninx, Brenda W.;Pergadia, Michele L.;Pericak-Vance, Margaret A.;Pickard, Benjamin S.;Pimm, Jonathan;Piven, Joseph;Posthuma, Danielle;Potash, James B.;Poustka, Fritz;Propping, Peter;Puri, Vinay;Quested, Digby J.;Quinn, Emma M.;Antoni Ramos-Quiroga, Josep;Rasmussen, Henrik B.;Raychaudhuri, Soumya;Rehnstroem, Karola;Reif, Andreas;Ribases, Marta;Rice, John P.;Rietschel, Marcella;Roeder, Kathryn;Roeyers, Herbert;Rossin, Lizzy;Rothenberger, Aribert;Rouleau, Guy;Ruderfer, Douglas;Rujescu, Dan;Sanders, Alan R.;Sanders, Stephan J.;Santangelo, Susan L.;Sergeant, Joseph A.;Schachar, Russell;Schalling, Martin;Schatzberg, Alan F.;Scheftner, William A.;Schellenberg, Gerard D.;Scherer, Stephen W.;Schork, Nicholas J.;Schulze, Thomas G.;Schumacher, Johannes;Schwarz, Markus;Scolnick, Edward;Scott, Laura J.;Shi, Jianxin;Shilling, Paul D.;Shyn, Stanley I.;Silverman, Jeremy M.;Slager, Susan L.;Smalley, Susan L.;Smit, Johannes H.;Smith, Erin N.;Sonuga-Barke, Edmund J. S.;St Clair, David;State, Matthew;Steffens, Michael;Steinhausen, Hans-Christoph;Strauss, John S.;Strohmaier, Jana;Stroup, T. Scott;Sutcliffe, James S.;Szatmari, Peter;Szelinger, Szabocls;Thirumalai, Srinivasa;Thompson, Robert C.;Todorov, Alexandre A.;Tozzi, Federica;Treutlein, Jens;Uhr, Manfred;van den Oord, Edwin J. C. G.;Van Grootheest, Gerard;Van Os, Jim;Vicente, Astrid M.;Vieland, Veronica J.;Vincent, John B.;Visscher, Peter M.;Walsh, Christopher A.;Wassink, Thomas H.;Watson, Stanley J.;Weissman, Myrna M.;Werge, Thomas;Wienker, Thomas F.;Wijsman, Ellen M.;Willemsen, Gonneke;Williams, Nigel;Willsey, A. Jeremy;Witt, Stephanie H.;Xu, Wei;Young, Allan H.;Yu, Timothy W.;Zammit, Stanley;Zandi, Peter P.;Zhang, Peng;Zitman, Frans G.;Zoellner, Sebastian;Devlin, Bernie;Kelsoe, John R.;Sklar, Pamela;Daly, Mark J.;O'Donovan, Michael C.;Craddock, Nicholas;Sullivan, Patrick F.;Smoller, Jordan W.;Kendler, Kenneth S.;Wray, Naomi R.
通讯作者：
Wray, Naomi R.
影响因子：
3.5
作者：
Dorajoo, Rajkumar;Sun, Ye;Friedlander, Yechiel
通讯作者：
Friedlander, Yechiel