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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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.

Amare, Azmeraw T (author)

Schubert, Klaus Oliver (author)

Hou, Liping (author)

Clark, Scott R (author)

Papiol, Sergi (author)

Heilbronner, Urs (author)

Degenhardt, Franziska (author)

Tekola-Ayele, Fasil (author)

Hsu, Yi-Hsiang (author)

Shekhtman, Tatyana (author)

Adli, Mazda (author)

Akula, Nirmala (author)

Akiyama, Kazufumi (author)

Ardau, Raffaella (author)

Arias, Bárbara (author)

Aubry, Jean-Michel (author)

Backlund, Lena (author): Karolinska Institutet

Bhattacharjee, Abesh Kumar (author)

Bellivier, Frank (author)

Benabarre, Antonio (author)

Bengesser, Susanne (author)

Biernacka, Joanna M (author)

Birner, Armin (author)

Brichant-Petitjean, Clara (author)

Cervantes, Pablo (author)

Chen, Hsi-Chung (author)

Chillotti, Caterina (author): Karolinska Institutet

Cichon, Sven (author)

Cruceanu, Cristiana (author)

Czerski, Piotr M (author)

Dalkner, Nina (author)

Dayer, Alexandre (author)

Del Zompo, Maria (author)

DePaulo, J Raymond (author)

Étain, Bruno (author)

Falkai, Peter (author)

Forstner, Andreas J (author)

Frisen, Louise (author): Karolinska Institutet

Frye, Mark A (author)

Fullerton, Janice M (author)

Gard, Sébastien (author)

Garnham, Julie S (author)

Goes, Fernando S (author)

Grigoroiu-Serbanescu, Maria (author)

Grof, Paul (author)

Hashimoto, Ryota (author)

Hauser, Joanna (author)

Herms, Stefan (author)

Hoffmann, Per (author)

Hofmann, Andrea (author)

Jamain, Stephane (author)

Jiménez, Esther (author)

Kahn, Jean-Pierre (author)

Kassem, Layla (author)

Kuo, Po-Hsiu (author)

Kato, Tadafumi (author)

Kelsoe, John (author)

Kittel-Schneider, Sarah (author)

Kliwicki, Sebastian (author)

König, Barbara (author)

Kusumi, Ichiro (author)

Laje, Gonzalo (author)

Landén, Mikael, 1966 (author): Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry

Lavebratt, Catharina (author)

Leboyer, Marion (author)

Leckband, Susan G (author)

Tortorella, Alfonso (author)

Manchia, Mirko (author): Karolinska Institutet

Martinsson, Lina (author): Karolinska Institutet

McCarthy, Michael J (author)

McElroy, Susan (author)

Colom, Francesc (author)

Mitjans, Marina (author)

Mondimore, Francis M (author)

Monteleone, Palmiero (author)

Nievergelt, Caroline M (author)

Nöthen, Markus M (author)

Novák, Tomas (author)

O'Donovan, Claire (author)

Ozaki, Norio (author)

Ösby, Urban (author)

Pfennig, Andrea (author)

Potash, James B (author)

Reif, Andreas (author)

Reininghaus, Eva (author)

Rouleau, Guy A (author)

Rybakowski, Janusz K (author)

Schalling, Martin (author)

Schofield, Peter R (author)

Schweizer, Barbara W (author)

Severino, Giovanni (author)

Shilling, Paul D (author)

Shimoda, Katzutaka (author)

Simhandl, Christian (author)

Slaney, Claire M (author)

Squassina, Alessio (author)

Stamm, Thomas (author)

Stopkova, Pavla (author)

Maj, Mario (author)

Turecki, Gustavo (author)

Vieta, Eduard (author)

Volkert, Julia (author)

Witt, Stephanie (author)

Wright, Adam (author)

Zandi, Peter P (author)

Mitchell, Philip B (author)

Bauer, Michael (author)

Alda, Martin (author)

Rietschel, Marcella (author)

McMahon, Francis J (author)

Schulze, Thomas G (author)

Baune, Bernhard T (author)

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(creator_code:org_t)

2017-11-09
2018
English.
In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74

Related links:: https://jamanetwork....; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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).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.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.Treatment response to lithium was 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.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 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.

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By the author/editor: Amare, Azmeraw T; Schubert, Klaus ...; Hou, Liping; Clark, Scott R; Papiol, Sergi; Heilbronner, Urs; show more...; Degenhardt, Fran ...; Tekola-Ayele, Fa ...; Hsu, Yi-Hsiang; Shekhtman, Tatya ...; Adli, Mazda; Akula, Nirmala; Akiyama, Kazufum ...; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Mich ...; Backlund, Lena; Bhattacharjee, A ...; Bellivier, Frank; Benabarre, Anton ...; Bengesser, Susan ...; Biernacka, Joann ...; Birner, Armin; Brichant-Petitje ...; Cervantes, Pablo; Chen, Hsi-Chung; Chillotti, Cater ...; Cichon, Sven; Cruceanu, Cristi ...; Czerski, Piotr M; Dalkner, Nina; Dayer, Alexandre; Del Zompo, Maria; DePaulo, J Raymo ...; Étain, Bruno; Falkai, Peter; Forstner, Andrea ...; Frisen, Louise; Frye, Mark A; Fullerton, Janic ...; Gard, Sébastien; Garnham, Julie S; Goes, Fernando S; Grigoroiu-Serban ...; Grof, Paul; Hashimoto, Ryota; Hauser, Joanna; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierr ...; Kassem, Layla; Kuo, Po-Hsiu; Kato, Tadafumi; Kelsoe, John; Kittel-Schneider ...; Kliwicki, Sebast ...; König, Barbara; Kusumi, Ichiro; Laje, Gonzalo; Landén, Mikael, ...; Lavebratt, Catha ...; Leboyer, Marion; Leckband, Susan ...; Tortorella, Alfo ...; Manchia, Mirko; Martinsson, Lina; McCarthy, Michae ...; McElroy, Susan; Colom, Francesc; Mitjans, Marina; Mondimore, Franc ...; Monteleone, Palm ...; Nievergelt, Caro ...; Nöthen, Markus M; Novák, Tomas; O'Donovan, Clair ...; Ozaki, Norio; Ösby, Urban; Pfennig, Andrea; Potash, James B; Reif, Andreas; Reininghaus, Eva; Rouleau, Guy A; Rybakowski, Janu ...; Schalling, Marti ...; Schofield, Peter ...; Schweizer, Barba ...; Severino, Giovan ...; Shilling, Paul D; Shimoda, Katzuta ...; Simhandl, Christ ...; Slaney, Claire M; Squassina, Aless ...; Stamm, Thomas; Stopkova, Pavla; Maj, Mario; Turecki, Gustavo; Vieta, Eduard; Volkert, Julia; Witt, Stephanie; Wright, Adam; Zandi, Peter P; Mitchell, Philip ...; Bauer, Michael; Alda, Martin; Rietschel, Marce ...; McMahon, Francis ...; Schulze, Thomas ...; Baune, Bernhard ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Psychiatry

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

Articles in the publication: JAMA psychiatry

By the university: University of Gothenburg; Karolinska Institutet

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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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