Polygenic risk score prediction of antipsychotic dosage in schizophrenia

被引：21
作者：
Hettige, Nuwan C. [1 ,2 ]
Cole, Christopher B. [1 ,3 ]
Khalid, Sarah [2 ]
De Luca, Vincenzo [1 ,2 ,4 ]
机构：
[1] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
[2] Ctr Addict & Mental Hlth, EEG & Genet Unit, 250 Coll St, Toronto, ON M5T 1R8, Canada
[3] Univ Ottawa, 75 Laurier Ave E, Ottawa, ON K1N 6N5, Canada
[4] Univ Toronto, Dept Psychiat, 250 Coll St, Toronto, ON M5T 1R8, Canada
来源：
SCHIZOPHRENIA RESEARCH | 2016年 / 170卷 / 2-3期
关键词：
Polygenic risk score; Antipsychotic dosage; Schizophrenia; Chlorpromazine equivalents; Defined daily dose; GENOME-WIDE ASSOCIATION; PSYCHOSIS; CONTINUUM; SYMPTOMS;
D O I：
10.1016/j.schres.2015.12.015
中图分类号：
R749 [精神病学];
学科分类号：
100205 ;
摘要：
Objective: Genetic variants have yet to be identified as reliable predictors of antipsychotic dosage. The purpose of this study is to quantify significant genetic risk variants prioritized from the Psychiatric GWAS Consortium (PGC2) study for schizophrenia as a polygenic score to test our hypothesis that it may represent symptom severity in patients and therefore predict antipsychotic dosage. Methods: Antipsychotic medication and dosage were collected in our sample of 83 patients with schizophrenia spectrum disorders of a homogeneous European background. Antipsychotic dosage was standardized according to the Product Monograph (PM%), chlorpromazine equivalents (CPZe), and Defined Daily Dose (DDD). We calculated polygenic risk scores (PRS) for the significant risk loci identified from the PGC2 GWAS to predict dosage using a linear regression model. Results: In our analysis, the PRS showed no significant association with PM%, CPZe, and DDD dosage. Considering symptom severity and overall functioning, our PRS was similarly not significantly associated with Global Assessment of Functioning (GAF) scores. Discussion: Our results do not provide evidence for a polygenic inheritance of schizophrenia that influences levels of antipsychotic dosage. To the best of our knowledge, this is one of the first studies of its kind to use the PRS from the PGC2 significant risk variants to predict a clinically relevant phenotype. The PRS offers a novel approach to analyzing the genetic liability for many clinically relevant phenotypes in schizophrenia. (c) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码：265 / 270
页数：6
相关论文
共 35 条
[21]  
Peralta V, 2007, WORLD PSYCHIATRY, V6, P36
[22]   Genetics and intelligence differences: five special findings [J].
Plomin, R. ;
Deary, I. J. .
MOLECULAR PSYCHIATRY, 2015, 20 (01) :98-108
[23]   PLINK: A tool set for whole-genome association and population-based linkage analyses [J].
Purcell, Shaun ;
Neale, Benjamin ;
Todd-Brown, Kathe ;
Thomas, Lori ;
Ferreira, Manuel A. R. ;
Bender, David ;
Maller, Julian ;
Sklar, Pamela ;
de Bakker, Paul I. W. ;
Daly, Mark J. ;
Sham, Pak C. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (03) :559-575
[24]   Common polygenic variation contributes to risk of schizophrenia and bipolar disorder [J].
Purcell, Shaun M. ;
Wray, Naomi R. ;
Stone, Jennifer L. ;
Visscher, Peter M. ;
O'Donovan, Michael C. ;
Sullivan, Patrick F. ;
Sklar, Pamela ;
Ruderfer, Douglas M. ;
McQuillin, Andrew ;
Morris, Derek W. ;
O'Dushlaine, Colm T. ;
Corvin, Aiden ;
Holmans, Peter A. ;
Macgregor, Stuart ;
Gurling, Hugh ;
Blackwood, Douglas H. R. ;
Craddock, Nick J. ;
Gill, Michael ;
Hultman, Christina M. ;
Kirov, George K. ;
Lichtenstein, Paul ;
Muir, Walter J. ;
Owen, Michael J. ;
Pato, Carlos N. ;
Scolnick, Edward M. ;
St Clair, David ;
Williams, Nigel M. ;
Georgieva, Lyudmila ;
Nikolov, Ivan ;
Norton, N. ;
Williams, H. ;
Toncheva, Draga ;
Milanova, Vihra ;
Thelander, Emma F. ;
Sullivan, Patrick ;
Kenny, Elaine ;
Quinn, Emma M. ;
Choudhury, Khalid ;
Datta, Susmita ;
Pimm, Jonathan ;
Thirumalai, Srinivasa ;
Puri, Vinay ;
Krasucki, Robert ;
Lawrence, Jacob ;
Quested, Digby ;
Bass, Nicholas ;
Crombie, Caroline ;
Fraser, Gillian ;
Kuan, Soh Leh ;
Walker, Nicholas .
NATURE, 2009, 460 (7256) :748-752
[25]  
REGIER DA, 1990, JAMA-J AM MED ASSOC, V264, P2511
[26]  
Repchinsky C., 2012, CANADIAN DRUG REFERE
[27]   Biological insights from 108 schizophrenia-associated genetic loci [J].
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 .
NATURE, 2014, 511 (7510) :421-+
[28]  
Sarpal D. K., 2015, AM J PSYCHIAT
[29]   Antipsychotic Treatment and Functional Connectivity of the Striatum in First-Episode Schizophrenia [J].
Sarpal, Deepak K. ;
Robinson, Delbert G. ;
Lencz, Todd ;
Argyelan, Miklos ;
Ikuta, Toshikazu ;
Karlsgodt, Katherine ;
Gallego, Juan A. ;
Kane, John M. ;
Szeszko, Philip R. ;
Malhotra, Anil K. .
JAMA PSYCHIATRY, 2015, 72 (01) :5-13
[30]   Magnetic Resonance Imaging Predictors of Treatment Response in First-Episode Schizophrenia [J].
Szeszko, Philip R. ;
Narr, Katherine L. ;
Phillips, Owen R. ;
McCormack, Joanne ;
Sevy, Serge ;
Gunduz-Bruce, Handan ;
Kane, John M. ;
Bilder, Robert M. ;
Robinson, Delbert G. .
SCHIZOPHRENIA BULLETIN, 2012, 38 (03) :569-578
1234