Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.
Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.
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多发性硬化症和精神分裂症之间的遗传多效性，但不是躁郁症：免疫相关基因基因座的差异参与。
DOI：
10.1038/mp.2013.195
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发表时间：
2015-02
影响因子：
11
通讯作者：
Dale, A. M.
中科院分区：
文献类型：
--
作者：
Andreassen, O. A.;Harbo, H. F.;Wang, Y.;Thompson, W. K.;Schork, A. J.;Mattingsdal, M.;Zuber, V.;Bettella, F.;Ripke, S.;Kelsoe, J. R.;Kendler, K. S.;O'Donovan, M. C.;Sklar, P.;McEvoy, L. K.;Desikan, R. S.;Lie, B. A.;Djurovic, S.;Dale, A. M.
越来越多的证据表明精神分裂症（SCZ）中存在免疫异常，最近的全基因组关联研究（GWAS）已经确定了与SCZ相关的免疫相关单核苷酸多态性（snp）。使用条件错误发现率（FDR）方法，我们评估了与SCZ （n=21 856）和多发性硬化症（n=43 879）相关的snp的多效性，多发性硬化症是一种中枢神经系统的炎症性脱髓鞘疾病。由于SCZ和双相情感障碍（BD）表现出大量的临床和遗传重叠，我们还研究了BD和MS之间的多效性（n= 16731）。我们发现SCZ和MS之间存在显著的遗传重叠，并鉴定出21个与SCZ相关的独立基因座，这些基因座与MS相关。重要的是，我们检测到相同的人类白细胞抗原（HLA）等位基因参与了SCZ和MS，但相关HLA等位基因的作用方向相反（即MS风险等位基因与SCZ风险降低相关）。相比之下，我们没有发现BD和MS之间的遗传重叠，综合考虑，我们的研究结果表明SCZ和MS之间存在遗传多效性，并提示MHC信号可能区分SCZ和BD易感性。
Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21 856) and multiple sclerosis (MS) (n=43 879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16 731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.
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影响因子：
30.8
作者：
Ripke, Stephan;O'Dushlaine, Colm;Chambert, Kimberly;Moran, Jennifer L.;Kaehler, Anna K.;Akterin, Susanne;Bergen, Sarah E.;Collins, Ann L.;Crowley, James J.;Fromer, Menachem;Kim, Yunjung;Lee, Sang Hong;Magnusson, Patrik K. E.;Sanchez, Nick;Stahl, Eli A.;Williams, Stephanie;Wray, Naomi R.;Xia, Kai;Bettella, Francesco;Borglum, Anders D.;Bulik-Sullivan, Brendan K.;Cormican, Paul;Craddock, Nick;de Leeuw, Christiaan;Durmishi, Naser;Gill, Michael;Golimbet, Vera;Hamshere, Marian L.;Holmans, Peter;Hougaard, David M.;Kendler, Kenneth S.;Lin, Kuang;Morris, Derek W.;Mors, Ole;Mortensen, Preben B.;Neale, Benjamin M.;O'Neill, Francis A.;Owen, Michael J.;Milovancevic, Milica Pejovic;Posthuma, Danielle;Powell, John;Richards, Alexander L.;Riley, Brien P.;Ruderfer, Douglas;Rujescu, Dan;Sigurdsson, Engilbert;Silagadze, Teimuraz;Smit, August B.;Stefansson, Hreinn;Steinberg, Stacy;Suvisaari, Jaana;Tosato, Sarah;Verhage, Matthijs;Walters, James T.;Bramon, Elvira;Corvin, Aiden P.;O'Donovan, Michael C.;Stefansson, Kari;Scolnick, Edward;Purcell, Shaun;McCarroll, Steven A.;Sklar, Pamela;Hultman, Christina M.;Sullivan, Patrick F.
通讯作者：
Sullivan, Patrick F.
影响因子：
16.2
作者：
Shatz, Carla J.
通讯作者：
Shatz, Carla J.
DOI：
10.1176/appi.ajp.2010.10091340
发表时间：
2011-03
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Gershon ES;Alliey-Rodriguez N;Liu C
通讯作者：
Liu C
DOI：
10.1016/j.jaac.2010.06.008
发表时间：
2010-09
影响因子：
13.3
作者：
Neale BM;Medland SE;Ripke S;Asherson P;Franke B;Lesch KP;Faraone SV;Nguyen TT;Schäfer H;Holmans P;Daly M;Steinhausen HC;Freitag C;Reif A;Renner TJ;Romanos M;Romanos J;Walitza S;Warnke A;Meyer J;Palmason H;Buitelaar J;Vasquez AA;Lambregts-Rommelse N;Gill M;Anney RJ;Langely K;O'Donovan M;Williams N;Owen M;Thapar A;Kent L;Sergeant J;Roeyers H;Mick E;Biederman J;Doyle A;Smalley S;Loo S;Hakonarson H;Elia J;Todorov A;Miranda A;Mulas F;Ebstein RP;Rothenberger A;Banaschewski T;Oades RD;Sonuga-Barke E;McGough J;Nisenbaum L;Middleton F;Hu X;Nelson S;Psychiatric GWAS Consortium: ADHD Subgroup
通讯作者：
Psychiatric GWAS Consortium: ADHD Subgroup
影响因子：
30.8
作者：
Liu, Jimmy Z.;Hov, Johannes Roksund;Folseraas, Trine;Ellinghaus, Eva;Rushbrook, Simon M.;Doncheva, Nadezhda T.;Andreassen, Ole A.;Weersma, Rinse K.;Weismueller, Tobias J.;Eksteen, Bertus;Invernizzi, Pietro;Hirschfield, Gideon M.;Gotthardt, Daniel Nils;Pares, Albert;Ellinghaus, David;Shah, Tejas;Juran, Brian D.;Milkiewicz, Piotr;Rust, Christian;Schramm, Christoph;Mueller, Tobias;Srivastava, Brijesh;Dalekos, Georgios;Noethen, Markus M.;Herms, Stefan;Winkelmann, Juliane;Mitrovic, Mitja;Braun, Felix;Ponsioen, Cyriel Y.;Croucher, Peter J. P.;Sterneck, Martina;Teufel, Andreas;Mason, Andrew L.;Saarela, Janna;Leppa, Virpi;Dorfman, Ruslan;Alvaro, Domenico;Floreani, Annarosa;Onengut-Gumuscu, Suna;Rich, Stephen S.;Thompson, Wesley K.;Schork, Andrew J.;Naess, Sigrid;Thomsen, Ingo;Mayr, Gabriele;Koenig, Inke R.;Hveem, Kristian;Cleynen, Isabelle;Gutierrez-Achury, Javier;Ricano-Ponce, Isis;van Heel, David;Bjoernsson, Einar;Sandford, Richard N.;Durie, Peter R.;Melum, Espen;Vatn, Morten H.;Silverberg, Mark S.;Duerr, Richard H.;Padyukov, Leonid;Brand, Stephan;Sans, Miquel;Annese, Vito;Achkar, Jean-Paul;Boberg, Kirsten Muri;Marschall, Hanns-Ulrich;Chazouilleres, Olivier;Bowlus, Christopher L.;Wijmenga, Cisca;Schrumpf, Erik;Vermeire, Severine;Albrecht, Mario;Rioux, John D.;Alexander, Graeme;Bergquist, Annika;Cho, Judy;Schreiber, Stefan;Manns, Michael P.;Farkkila, Martti;Dale, Anders M.;Chapman, Roger W.;Lazaridis, Konstantinos N.;Franke, Andre;Anderson, Carl A.;Karlsen, Tom H.
通讯作者：
Karlsen, Tom H.