Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort.
Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort.
复制标题
抗精神病药的症状和治疗反应分析的多基因风险评分分析精神病队列的抗精神病药。
DOI：
10.1038/s41398-018-0230-7
复制
发表时间：
2018-08-31
影响因子：
6.8
通讯作者：
Breen G
中科院分区：
文献类型：
--
作者：
Santoro ML;Ota V;de Jong S;Noto C;Spindola LM;Talarico F;Gouvea E;Lee SH;Moretti P;Curtis C;Patel H;Newhouse S;Carvalho CM;Gadelha A;Cordeiro Q;Bressan RA;Belangero SI;Breen G
在这项研究中，我们的目的是测试精神分裂症（SCZ）多基因风险评分（PRS）是否与临床症状（a）精神病首次发作治疗前（FEP），（B）在开始利培酮治疗后9周（FEP-9 W）和（c）与利培酮的反应。我们对60例未接受过抗精神病药物治疗的FEP患者进行了详细的临床评估，这些患者再次接受了9周的利培酮标准化治疗。在血液收集和DNA分离后，使用Illumina PsychArrayChip对样品进行基因分型，然后进行插补。为了计算PRS，我们使用来自精神病基因组学联盟wave-2 SCZ组的最新可用GWAS汇总统计作为训练集。我们使用Poisson回归来检验PRS和临床测量之间的关联，校正四个主成分（基因分型）。我们认为p值< 0.0014（Bonferroni校正）具有显著性。首先，我们验证了精神分裂症PRS也能够区分这种东南部巴西样本中的病例和对照，解释了北方欧洲人群中观察到的相似方差。此外，在病例内分析中，我们发现PRS与基线（治疗前）症状显著相关，如较低的临床总体功能评估（−GAF），较高的抑郁症状和较高的衍生兴奋因子评分。经过9周的规范化治疗后，GAF和兴奋因子的相关性消失，而抑郁症状与PRS呈负相关。我们的结论是，药物（和其他治疗）可能会混淆试图了解病因学的影响，多基因风险评分。这些结果强调了研究精神分裂症和其他疾病的重要性，治疗前了解多基因风险和表型特征之间的关系。
In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed. To calculate PRS, we used the latest available GWAS summary statistics from the Psychiatric Genomics Consortium wave-2 SCZ group as a training set. We used Poisson regression to test association between PRS and clinical measurements correcting for the four principal components (genotyping). We considered a p-value < 0.0014 (Bonferroni correction) as significant. First, we verified that the schizophrenia PRS was also able to distinguish cases from controls in this south-eastern Brazilian sample, with a similar variance explained to that seen in Northern European populations. In addition, within-cases analyses, we found that PRS is significantly correlated with baseline (pre-treatment) symptoms, as measured by lower clinical global assessment of functioning (−GAF), higher depressive symptoms and higher scores on a derived excitement factor. After standardized treatment for nine weeks, the correlation with GAF and the excitement factor disappeared while depressive symptoms became negatively associated with PRS. We conclude that drug (and other treatments) may confound attempts to understand the aetiological influence on symptomatology of polygenic risk scores. These results highlight the importance of studying schizophrenia, and other disorders, pre-treatment to understand the relationship between polygenic risk and phenotypic features.
登录
查看更多内容
影响因子：
7
作者：
Wray, Naomi R.;Goddard, Michael E.;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
4.8
作者：
Fuste, Montserrat;Pinacho, Raquel;Ramos, Belen
通讯作者：
Ramos, Belen
影响因子：
--
作者：
Sullivan, PF;Kendler, KS;Neale, MC
通讯作者：
Neale, MC
影响因子：
4.5
作者：
Wallwork, R. S.;Fortgang, R.;Hashimoto, R.;Weinberger, D. R.;Dickinson, D.
通讯作者：
Dickinson, D.
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.