Browsing by Subject "BIPOLAR DISORDER"

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  • Schizophrenia Working Group of the Psychiatric Genomics Consortium; Ni, Guiyan; Gratten, Jacob; Wray, Naomi R.; Lee, Sang Hong; Eriksson, Johan Gunnar; Paunio, Tiina Maria; Pietiläinen, Olli Kalevi; Palotie, Aarno Veikko (2018)
    Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.
  • Mantyla, Teemu; Mantere, Outi; Raij, Tuukka T.; Kieseppa, Tuula; Laitinen, Hanna; Leiviska, Jaana; Torniainen, Minna; Tuominen, Lauri; Vaarala, Outi; Suvisaari, Jaana (2015)
    First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1-and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFa, CXCL1, CCL7, IFN-alpha 2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum lan association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.evel of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate
  • Schwarz, Emanuel; Maukonen, Johanna; Hyytiäinen, Tiina; Kieseppä, Tuula; Oresic, Matej; Sabunciyan, Sarven; Mantere, Outi; Saarela, Maria; Yolken, Robert; Suvisaari, Jaana (2018)
    The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12 months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12 months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission. (C) 2017 Elsevier B.V. All rights reserved.
  • Brainstorm Consortium; Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J.; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A.; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H.; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-Francois; Duron, Emmanuelle; Vardarajan, Badri N.; Reitz, Christiane; Goate, Alison M.; Huentelman, Matthew J.; Kamboh, M. Ilyas; Larson, Eric B.; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A.; Palta, Priit; Wedenoja, Juho; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Kurki, Mitja I.; Hämäläinen, Eija; Kaprio, Jaakko; Metspalu, Andres; Keski-Rahkonen, Anna; Raevuori, Anu; Ripatti, Samuli; Lönnqvist, Jouko; Daly, Mark; Palotie, Aarno; Neale, Benjamin M. (2018)
    Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
  • Kovanen, Leena; Saarikoski, Sirkku Talvikki; Aromaa, Arpo; Lönnqvist, Jouko; Partonen, Timo (2010)
  • Stubbs, Brendon; Vancampfort, Davy; Mänty, Minna; Svärd, Anna; Rahkonen, Ossi; Lahti, Jouni (2017)
    This study aimed to examine the bidirectional relationship between psychotropic medication use and changes in leisure-time physical activity (LTPA) among a population cohort study. Phase 1 data were collected by mail surveys in 2000-2002 among 40-60-year-old employees of the City of Helsinki, Finland, and phase 2 follow up survey was conducted in 2007. Based on self-report, the respondents were classified as inactive and active (.14.75 MET-hours/week) at the phases 1 and 2. Hazard ratios (HR) were calculated for subsequent (2007-10) psychotropic medication purchasing according to changes in physical activity (phases 1-2). Odds ratios (OR) for physical inactivity at phase 2 were calculated according to the amount of psychotropic medication between phases 1-2. Overall, 5361 respondents were included (mean age 50 years, 80% women). Compared with the persistently active, the persistently inactive, those decreasing and adopting LTPA had an increased risk for psychotropic medication. Only the persistently inactive remained at increased risk for psychotropic medication use, following the adjustment for prior psychotropic medication use. Compared with those having no medication, the risk for physical inactivity increased as the psychotropic medication increased. Our data suggest that physical activity has an important role in maintaining wellbeing and reducing psychotropic medication usage.
  • Lindgren, Maija; Mäntylä, Teemu; Rikandi, Eva; Torniainen-Holm, Minna; Morales-Munoz, Isabel; Kieseppä, Tuula; Mantere, Outi; Suvisaari, Jaana (2017)
    In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP.
  • Bartels, Meike; Hendriks, Anne; Mauri, Matteo; Krapohl, Eva; Whipp, Alyce; Bolhuis, Koen; Conde, Lucia Colodro; Luningham, Justin; Ip, Hill Fung; Hagenbeek, Fiona; Roetman, Peter; Gatej, Raluca; Lamers, Audri; Nivard, Michel; van Dongen, Jenny; Lu, Yi; Middeldorp, Christel; van Beijsterveldt, Toos; Vermeiren, Robert; Hankemeijer, Thomas; Kluft, Cees; Medland, Sarah; Lundstrom, Sebastian; Rose, Richard; Pulkkinen, Lea; Vuoksimaa, Eero; Korhonen, Tellervo; Martin, Nicholas G.; Lubke, Gitta; Finkenauer, Catrin; Fanos, Vassilios; Tiemeier, Henning; Lichtenstein, Paul; Plomin, Robert; Kaprio, Jaakko; Boomsma, Dorret I. (2018)
    Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
  • Maksimovic, Milica; Vekovischeva, Olga Y.; Aitta-aho, Teemu; Korpi, Esa R. (2014)
  • Kovanen, Leena; Donner, Kati; Kaunisto, Mari; Partonen, Timo (2016)
    Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single-nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self-report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2). (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Yu, Rongqin; Aaltonen, Mikko; Branje, Susan; Ristikari, Tiina; Meeus, Wim; Salmela-Aro, Katariina; Goodwin, Guy M.; Fazel, Seena (2017)
    Objective: Despite recent research demonstrating associations between violence and depression in adults, links in adolescents are uncertain. This study aims to assess the longitudinal associations between young people's depression and later violent outcomes. Method: We used data from three cohorts with different measurements of depression exposures and subsequent violent outcomes. In a Dutch community cohort Research on Adolescent Development And Relationships (RADAR; N = 623) and a population-based British birth cohort Avon Longitudinal Study of Parents and Children (ALSPAC; N = 4,030), we examined the longitudinal links between adolescent depressive symptoms and violent behaviors from age 13 to 17 years. In a total Finnish birth cohort (FBC 1987; N = 57,526), we estimated risk of violent convictions in individuals clinically diagnosed with depression from age 15 to 27 years. Results: During a mean follow-up period of 4 years, the adjusted odds ratio (aOR) of violent behaviors per unit of increase in depressive symptoms was 1.7 (95% CI = 1.2-2.5) in the Dutch RADAR community sample and 1.8 (95% CI = 1.4-2.3) in the British ALSPAC birth cohort. In the FBC 1987 cohort, the aOR of violent convictions was 2.1 (95% CI = 1.7-2.7) among individuals with a depression diagnosis compared with general population controls without depression. All risk estimates were adjusted for family socioeconomic status and previous violence. Conclusion: Consistent findings across three longitudinal studies suggest that clinical guidelines should consider recommending risk assessment for violence in young people with depression. The benefits of targeting risk management in subgroups by gender need further investigation.
  • Soininen, Paivi; Putkonen, Hanna; Joffe, Grigori; Korkeila, Jyrki; Puukka, Pauli; Pitkanen, Anneli; Valimaki, Maritta (2013)
  • Hakulinen, Christian; Elovainio, Marko; Arffman, Martti; Lumme, Sonja; Suokas, Kimmo; Pirkola, Sami; Keskimäki, Ilmo; Manderbacka, Kristiina; Böckerman, Petri (2020)
    Objective: Individuals with severe mental disorders have an impaired ability to work and are likely to receive income transfer payments as their main source of income. However, the magnitude of this phenomenon remains unclear. Using longitudinal population cohort register data, the authors conducted a case-control study to examine the levels of employment and personal income before and after a first hospitalization for a serious mental disorder. Methods: All individuals (N=50,551) who had been hospitalized for schizophrenia, other nonaffective psychosis, or bipolar disorder in Finland between 1988 and 2015 were identified and matched with five randomly selected participants who were the same sex and who had the same birth year and month. Employment status and earnings, income transfer payments, and total income in euros were measured annually from 1988 to 2015. Results: Individuals with serious mental disorders had notably low levels of employment before, and especially after, the diagnosis of a severe mental disorder. Their total income was mostly constituted of transfer payments, and this was especially true for those diagnosed as having schizophrenia. More than half of all individuals with a serious mental disorder did not have any employment earnings after they received the diagnosis. Conclusions: The current study shows how most individuals in Finland depend solely on income transfer payments after an onset of a severe mental disorder.
  • Baryshnikov, Ilya; Aaltonen, Kari; Suvisaari, Jaana; Koivisto, Maaria; Heikkinen, Martti; Joffe, Grigori; Isometsä, Erkki (2018)
    Background: Psychosis-like experiences (PEs) are common in patients with non-psychotic disorders. Several factors predict reporting of PEs in mood disorders, including mood-associated cognitive biases, anxiety and features of borderline personality disorder (BPD). Childhood traumatic experiences (CEs), often reported by patients with BPD, are an important risk factor for mental disorders. We hypothesized that features of BPD may mediate the relationship between CEs and PEs. In this study, we investigated the relationships between self-reported PEs, CEs and features of BPD in patients with mood disorders. Methods: As part of the Helsinki University Psychiatric Consortium study, McLean Screening Instrument (MSI), Community Assessment of Psychic Experiences (CAPE-42) and Trauma and Distress Scale (TADS) were filled in by patients with mood disorders (n = 282) in psychiatric care. Correlation coefficients between total scores of scales and their dimensions were estimated, multiple regression and mediation analyses were conducted. Results: Total scores of MSI correlated strongly with scores of the CAPE-42 dimension "frequency of positive symptoms" (rho = 0.56; p Conclusions: Self-reported cognitive-perceptual symptoms of BPD fully mediate, while affective, behavioural and interpersonal symptoms only partially mediate the relationships between CEs and PEs. Recognition of co-morbid features of BPD in patients with mood disorders reporting PEs is essential. (c) 2017 Elsevier Masson SAS. All rights reserved.
  • Cattaneo, Annamaria; Cattane, Nadia; Malpighi, Chiara; Czamara, Darina; Suarez, Anna; Mariani, Nicole; Kajantie, Eero; Luoni, Alessia; Eriksson, Johan G.; Lahti, Jari; Mondelli, Valeria; Dazzan, Paola; Räikkönen, Katri; Binder, Elisabeth B.; Riva, Marco A.; Pariante, Carmine M. (2018)
    To date, gene-environment (GxE) interaction studies in depression have been limited to hypothesis-based candidate genes, since genome-wide (GWAS)-based GxE interaction studies would require enormous datasets with genetics, environmental, and clinical variables. We used a novel, cross-species and cross-tissues "omics" approach to identify genes predicting depression in response to stress in GxE interactions. We integrated the transcriptome and miRNome profiles from the hippocampus of adult rats exposed to prenatal stress (PNS) with transcriptome data obtained from blood mRNA of adult humans exposed to early life trauma, using a stringent statistical analyses pathway. Network analysis of the integrated gene lists identified the Forkhead box protein O1 (FoxO1), Alpha-2-Macroglobulin (A2M), and Transforming Growth Factor Beta 1 (TGF-beta 1) as candidates to be tested for GxE interactions, in two GWAS samples of adults either with a range of childhood traumatic experiences (Grady Study Project, Atlanta, USA) or with separation from parents in childhood only (Helsinki Birth Cohort Study, Finland). After correction for multiple testing, a meta-analysis across both samples confirmed six FoxO1 SNPs showing significant GxE interactions with early life emotional stress in predicting depressive symptoms. Moreover, in vitro experiments in a human hippocampal progenitor cell line confirmed a functional role of FoxO1 in stress responsivity. In secondary analyses, A2M and TGF-beta 1 showed significant GxE interactions with emotional, physical, and sexual abuse in the Grady Study. We therefore provide a successful 'hypothesis-free' approach for the identification and prioritization of candidate genes for GxE interaction studies that can be investigated in GWAS datasets.
  • Varendi, Kärt; Mätlik, Kert; Andressoo, Jaan-Olle (2015)
    During the past decade, the identification of microRNA (miR) targets has become common laboratory practice, and various strategies are now used to detect interactions between miRs and their mRNA targets. However, the current lack of a standardized identification process often leads to incomplete and/or conflicting results. Here, we review the problems most commonly encountered when verifying miR-mRNA interactions, and we propose a workflow for future studies. To illustrate the challenges faced when validating a miR target, we discuss studies in which the regulation of brain-derived neurotrophic factor by miRs was investigated, and we highlight several controversies that emerged from these studies. Finally, we discuss the therapeutic use of miR inhibitors, and we discuss several questions that should be addressed before proceeding to preclinical testing.
  • Urrila, Anna S.; Hakkarainen, Antti; Castaneda, Anu; Paunio, Tiina; Marttunen, Mauri; Lundbom, Nina (2017)
    Aim: This study used proton magnetic resonance spectroscopy (H-1 MRS) to evaluate the neurochemistry of the frontal cortex in adolescents with symptoms of sleep and depression. Methods: Nineteen non-medicated adolescent boys (mean age 16.0 years; 9 clinical cases with depression/sleep symptoms and 10 healthy controls) underwent H-1 MRS at 3 T. MR spectra were acquired from the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex, and frontal white matter. Concentrations of N-acetyl aspartate, total creatine, choline-containing compounds, total glutamine plus glutamate, and myo-inositol (mI) were compared in the 2 subgroups, and correlated with sleep and clinical measures in the total sample. Sleep was assessed with self-report questionnaires and ambulatory polysomnography recordings. Results: Concentrations of mI were lower in both frontal cortical regions among the depressed adolescents than in controls. No statistically significant differences in other metabolite concentrations were observed between the subgroups. Frontal cortex mI concentrations correlated negatively with depression severity, subjective daytime sleepiness, insomnia symptoms, and the level of anxiety, and correlated positively with total sleep time and overall psychosocial functioning. The correlations between mI in the ACC and total sleep time as well as daytime sleepiness remained statistically significant when depression severity was controlled in the analyses. Conclusion: Lower frontal cortex ml may indicate a disturbed second messenger system. Frontal cortical mI may thus be linked to the pathophysiology of depression and concomitant sleep symptoms among maturing adolescents. Short sleep and daytime sleepiness may be associated with frontal cortex mI independently from depression. (C) 2017 S. Karger AG, Basel
  • McLaughlin, Russell L.; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R.; O'Brien, Margaret; Kahn, Rene S.; Ophoff, Roel A.; Goris, An; Bradley, Daniel G.; Al-Chalabi, Ammar; van den Berg, Leonard H.; Luykx, Jurjen J.; Hardiman, Orla; Veldink, Jan H.; Project MinE GWAS Consortium; Schizophrenia Working Grp Psychiat; Palotie, Aarno (2017)
    We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.
  • Chen, Jingchun; Bacanu, S. A.; Yu, H.; Zhao, Z.; Jia, P.; Kendler, K. S.; Kranzler, H. R.; Gelernter, J.; Farrer, L.; Minica, C.; Pool, R.; Milaneschi, Y.; Boomsma, D. I.; Penninx, B. W.; Tyndale, R. F.; Ware, J. J.; Vink, J. M.; Kaprio, Jaakko; Munafo, M.; Chen, X.; Ware, J. J.; Chen, X.; Vink, J. M.; Loukola, Anu; Minica, C.; Pool, R.; Milaneschi, Y.; Mangino, M.; Menni, C.; Chen, J.; Peterson, R.; Auro, Kirsi; Lyytikäinen, Leo-Pekka; Wedenoja, Juho; Stiby, A. I.; Hemani, G.; Willemsen, G.; Hottenga, J. J.; Korhonen, Tellervo; Heliövaara, Markku; Perola, Markus; Rose, R.; Paternoster, L.; Timpson, N.; Wassenaar, C. A.; Zhu, A. Z.; Smith, G. D.; Raitakari, Olli; Lehtimäki, Terho; Kähönen, Mika; Koskinen, Seppo; Spector, T.; Penninx, B. W.; Salomaa, Veikko; Boomsma, D. I.; Tyndale, R. F.; Munafo, M.; Ware, J. J.; Chen, X.; Vink, J. M.; Minica, C.; Chen, J.; Peterson, R.; Timpson, N.; Taylor, M.; Boomsma, D. I.; Munafo, M.; Maes, H.; Riley, B.; Kendler, K. S.; Gelernter, J.; Sherva, R.; Farrer, L.; Kranzler, H. R.; Maher, B.; Vanyukov, M. (2016)
    It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerstrom test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 x 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 x 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.
  • Ukkola-Vuoti, Liisa; Kanduri, Chakravarthi; Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lahdesmaki, Harri; Järvelä, Irma (2013)