دورية أكاديمية
Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study
| العنوان: | Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study |
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| المؤلفون: | Amare, AT, Schubert, KO, Hou, L, Clark, SR, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, Hsu, YH, Shekhtman, T, Adli, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, JM, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Brichant-Petitjean, C, Cervantes, P, Chen, HC, Chillotti, C, Cichon, S, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Del Zompo, M, DePaulo, JR, Étain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Herms, S, Hoffmann, P, Hofmann, A, Jamain, S, Jiménez, E, Kahn, JP, Kassem, L, Kuo, PH, Kato, T, Kelsoe, J, Kittel-Schneider, S, Kliwicki, S, König, B, Kusumi, I, Laje, G, Landén, M, Lavebratt, C, Leboyer, M, Leckband, SG, Tortorella, A, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nöthen, MM, Novák, T, O'Donovan, C, Ozaki, N, Ösby, U, Pfennig, A, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Maj, M, Turecki, G, Mitchell, Philip |
| المصدر: | urn:ISSN:2168-622X ; urn:ISSN:2168-6238 ; JAMA Psychiatry, 75, 1, 65-74 |
| بيانات النشر: | American Medical Association (AMA) |
| سنة النشر: | 2018 |
| المجموعة: | UNSW Sydney (The University of New South Wales): UNSWorks |
| مصطلحات موضوعية: | Schizophrenia, Serious Mental Illness, Human Genome, Brain Disorders, Clinical Research, Mental Health, Prevention, Genetics, 2 Aetiology, 2.1 Biological and endogenous factors, Adult, Bipolar Disorder, Female, Genetic Load, Genome-Wide Association Study, Genotype, HLA Antigens, Humans, Inflammation, Lithium Carbonate, Male, Middle Aged, Multifactorial Inheritance, Schizophrenic Psychology, Treatment Outcome, International Consortium on Lithium Genetics (ConLi+Gen), anzsrc-for: 1199 Other Medical and Health Sciences, anzsrc-for: 1701 Psychology, anzsrc-for: 1702 Cognitive Sciences |
| الوصف: | IMPORTANCE Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). OBJECTIVES To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. DESIGN, SETTING, AND PARTICIPANTS A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013.Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. MAIN OUTCOMES AND MEASURES Treatment response to lithiumwas defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. RESULTS Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 ? 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95%CI, 1.42-8.41) at the first decile to 2.03 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/1959.4/unsworks_48588Test; https://unsworks.unsw.edu.au/bitstreams/c2d312a8-c2c9-46f2-898f-65b5c79ce004/downloadTest; https://doi.org/10.1001/jamapsychiatry.2017.3433Test |
| DOI: | 10.1001/jamapsychiatry.2017.3433 |
| الإتاحة: | https://doi.org/10.1001/jamapsychiatry.2017.3433Test http://hdl.handle.net/1959.4/unsworks_48588Test https://unsworks.unsw.edu.au/bitstreams/c2d312a8-c2c9-46f2-898f-65b5c79ce004/downloadTest |
| حقوق: | open access ; https://purl.org/coar/access_right/c_abf2Test ; CC-BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; free_to_read |
| رقم الانضمام: | edsbas.367521E2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1001/jamapsychiatry.2017.3433 |
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