Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Kálmán, Jánoš; Papiol, Sergi; Forstner, Andreas J.; Heilbronner, Urs; Degenhardt, Franziska; Strohmaier, Jana; Adli, Mazda; Adorjan, Kristina; Akula, Nirmala; Alda, Martin; Anderson‐Schmidt, Heike; Andlauer, Till F. M.; Anghelescu, Ion; Ardau, Raffaella; Arias, Bárbara; Arolt, Volker; Aubry, Jean Michel; Backlund, Lena; Bartholdi, Kim; Bauer, Michael; Baune, Bernhard T.; Becker, Thomas; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M.; Birner, Armin; Brichant‐Petitjean, Clara; Budde, Monika; Cervantes, Pablo; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Colom, Francesc; Comes, Ashley L.; Cruceanu, Cristiana; Czerski, Piotr M.; Dannlowski, Udo; Dayer, Alexandre; Zompo, Maria Del; DePaulo, J. Raymond; Dietrich, Detlef E.; Étain, Bruno; Ethofer, Thomas; Falkai, Peter; Fallgatter, Andreas J.; Figge, Christian; Flatau, Laura; Folkerts, Here; Frisén, Louise; Frye, Mark A.; Fullerton, Janice M.; Gade, Katrin; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grigoroiu‐Serbanescu, Maria; Gryaznova, Anna; Hake, Maria; Hauser, Joanna; Herms, Stefan; Hoffmann, Per; Hou, Liping; Jäger, Markus; Jamain, Stéphane; Jiménez, Esther; Juckel, Georg; Kahn, Jean Pierre; Kassem, Layla; Kelsoe, John R.; Kittel‐Schneider, Sarah; Kliwicki, Sebastian; Klohn-Sagatholislam, Farah; Köller, Manfred; König, Barbara; Konrad, Carsten; Lackner, Nina; Laje, Gonzalo; Landén, Mikael; Lang, Fabian; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; Maj, Mario; Manchia, Mirko; Martinsson, Lina; McCarthy, Michael J.; McElroy, Susan L.; McMahon, Francis J.; Mitchell, Philip B.; Mitjans, Marina; Mondimore, Francis M.; Monteleone, Palmiero; Nieratschker, Vanessa; Nievergelt, Caroline M.; Novák, Tomáš; Ösby, Urban; Pfennig, Andrea; Potash, James B.; Reich‐Erkelenz, Daniela; Reif, Andreas; Reimer, Jens; Reininghaus, Eva; Reitt, Markus; Ripke, Stephan; Rouleau, Guy; Rybakowski, Janusz; Schalling, Martin; Scherk, Harald; Schmauß, Max; Schofield, Peter R.; Schubert, Klaus Oliver; Schulte, Eva C.; Schulz, Sybille; Senner, Fanny; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D.; Simhandl, Christian; Slaney, Claire; Spitzer, Carsten; Squassina, Alessio; Stamm, Thomas; Stegmaier, Sophia; Stierl, Sebastian; Stopková, Pavla; Thiel, Andreas; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Vieta, Eduard; Veeh, Julia; Hagen, Martin von; Wigand, Moritz E.; Wiltfang, Jens; Witt, Stephanie H.; Wright, Adam; Zandi, Peter P.; Zimmermann, Jörg; Nöthen, Markus M.; Rietschel, Marcella; Schulze, Thomas G.

doi:10.1111/bdi.12659

Cited by 26 publications

(23 citation statements)

References 32 publications

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“…Calafato and colleagues used, as mentioned before, the PGRS for schizophrenia to identify psychotic disorders [69] . The PGRS can also be used to investigate traits like age at onset e.g., Kalman and colleagues investigated the PGRS for schizophrenia and BD in synopsis with age at onset, but with negative results [72] . Groundbreaking results were also achieved by the PGC to either distinguish BD and schizophrenia and on the other hand to search for shared pathways-114 genome-wide significant loci were shared between schizophrenia and BD in a sample comprising of 53,555 individuals with BD or schizophrenia and 54,065 controls.…”

Section: Polygenic Risk Score For Schizophrenia In Bdmentioning

confidence: 99%

Polygenic Risk Scores and Bipolar Disorder

2018

J Psychiatry Brain Sci

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Bipolar disorder is an affective disorder with mood swings between the pole of depression and the pole of mania. The mechanism of those mood swings has not been completely elucidated yet. According to current scientific knowledge affective episodes are caused by a concatenation between a genetic predisposition and biopsychosocial triggers. Even though diverse genome wide associated gene variants (e.g., single nucleotide polymorphisms of CACNA1C, ANK3 or NCAN) were associated with Bipolar disorder in the last decade, there is still missing heritability. Thus, innovative approaches and endophenotypes of Bipolar disorder must be used to decipher the underlying disease mechanisms of Bipolar disorder. Recently, the Polygenic Risk Score for Schizophrenia was investigated in the lithium response endophenotype of Bipolar disorder. The polygenic score for Schizophrenia was inversely associated with the lithium response phenotype in study participants with Bipolar disorder. Furthermore, there are genetic overlaps between psychiatric diseases, which also demonstrates the importance of cross-disorder design studies to elucidate the missing heritability of Bipolar disorder.

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Section: Polygenic Risk Score For Schizophrenia In Bdmentioning

confidence: 99%

Polygenic Risk Scores and Bipolar Disorder

2018

J Psychiatry Brain Sci

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“…Such a PRS might, in turn, be relevant to be studied in interaction with environmental risk factors that increase the susceptibility to the phenotype and/or the severity of the phenotype. Even though few studies have been published yet, it is suggested that a high PRS‐BD might be associated with some indicators of the severity of the clinical expression in BD, such as the presence of psychotic features during mood episodes, while PRS‐BD has been suggested not to be associated with an earlier age at onset, another indicator of clinical severity …”

Section: Introductionmentioning

confidence: 99%

Childhood maltreatment and polygenic risk in bipolar disorders

et al. 2019

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Background Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P = .01), especially when considering emotional abuse (rho = −0.16, P = .001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.

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“…Moreover, one could argue that the higher percentage of females diagnosed with BD-II could interfere with the gender distribution of the samples analysed, and therefore be the cause of our ndings. However, of note, Bobo et al, 32 Buoli et al, 33 Karanti et al, 27 and Vieta et al, 34 had a higher proportion of BDI patients in their samples, and Kalman et al 36 only had BDI patients in their sample. Findings of a higher prevalence of female patients in these four studies could further support our hypothesis, being BDI the type of BD traditionally more commonly associated with equal prevalence in the two genders.…”

Section: Discussionmentioning

confidence: 90%

“…34 Another study collected data from the ConLiGen database (n = 2,563), 35 while the last one included data collected from ConLiGen, Bonn-Mannheim and PsyCourse databases (n = 1,995, BDI patients only). 36 Nine out of ten studies analysed samples of both BDI and BDII patients, while one study only analysed a sample of BDI patients. All the evaluated studies described the general distribution of their samples in terms of gender, reporting a higher prevalence of female patients, with female patient proportions ranging from 57•4% (RENDiBi Study) to 65•0% (WAVE-BD) (Figure 1a ).…”

Section: Resultsmentioning

confidence: 99%

Has Bipolar Disorder become a predominantly female gender related condition? Analysis of recently published large sample studies

Dell’Osso¹,

Cafaro

Ketter

2020

Preprint

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Bipolar Disorders are disabling and severe psychiatric disorders, commonly perceived as equally affecting both men and women. The prevalence of BD in the general population has been growing over the last decade, however, few epidemiological studies are available regarding BD gender distribution, leaving unanswered the question whether the often reported increment of BD diagnosis could be gender specific. In fact, BD in female patients can often be misdiagnosed as MDD, leaving such women non correctly treated for longer times than their male counterparts. From this perspective, we searched literature for large sample (>1000 subjects) studies conducted in the last decade (2010 onward) on BD patients. We included ten large sample studies that reported the gender distribution of their samples, and we therefore analysed them. Our results show a higher preponderance of female patients in every sample and sub-sample of BDI and BDII, supporting our hypothesis of an increase in BD diagnosis in females. BD in women presents with higher rates of rapid cycling, depressive polarity and suicide attempts, characteristics of non inferior severity compared to males; prompt recognition and adequate treatment of BD is therefore crucial to reduce risks and improve quality of life of affected women. In this regard, our results could lead the way for national or international epidemiological studies with the aim of more accurately assessing gender-specific prevalence of BD.

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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Cited by 26 publications

References 32 publications

Polygenic Risk Scores and Bipolar Disorder

Polygenic Risk Scores and Bipolar Disorder

Childhood maltreatment and polygenic risk in bipolar disorders

Has Bipolar Disorder become a predominantly female gender related condition? Analysis of recently published large sample studies

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