Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.


:Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10-10), SLC38A3 (Pbest = 5.7 × 10-10), and CABP1-ACADS (Pbest = 9.8 × 10-9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10-11) and between SCZ and BD in the JPN population (P ~ 10-40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ "risk" effect is shared with other psychiatric disorders even across populations.


Schizophr Bull


Schizophrenia bulletin


Ikeda M,Takahashi A,Kamatani Y,Momozawa Y,Saito T,Kondo K,Shimasaki A,Kawase K,Sakusabe T,Iwayama Y,Toyota T,Wakuda T,Kikuchi M,Kanahara N,Yamamori H,Yasuda Y,Watanabe Y,Hoya S,Aleksic B,Kushima I,Arai H,Takaki




Has Abstract


2019-06-18 00:00:00














  • Financial capacity in persons with schizophrenia and serious mental illness: clinical and research ethics aspects.

    abstract::In contrast with issues of consent capacity, financial capacity has received surprisingly little clinical or ethical attention in the psychiatric literature. Issues of financial capacity emerge frequently regarding clients with serious mental illness (SMI), and their resolution has practical and ethical significance f...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Marson DC,Savage R,Phillips J

    更新日期:2006-01-01 00:00:00

  • Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations.

    abstract::Neuroleptic drugs block brain dopamine receptors and are effective in treating psychoses of diverse origins. This finding has become a cornerstone of the dopamine theory of schizophrenia, but clinical studies relating schizophrenia, per se, to brain dopamine metabolism have ranged from controversial to negative. This ...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Maas JW,Bowden CL,Miller AL,Javors MA,Funderburg LG,Berman N,Weintraub ST

    更新日期:1997-01-01 00:00:00

  • The G72/G30 gene locus in psychiatric disorders: a challenge to diagnostic boundaries?

    abstract::In follow-up from evidence obtained in linkage studies, systematic linkage disequilibrium mapping within chromosomal region 13q33 has led to the identification of a schizophrenia susceptibility locus which harbors the genes G72 and G30. These association findings have been replicated in several independent schizophren...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Abou Jamra R,Schmael C,Cichon S,Rietschel M,Schumacher J,Nöthen MM

    更新日期:2006-10-01 00:00:00

  • Symptom Remission and Brain Cortical Networks at First Clinical Presentation of Psychosis: The OPTiMiSE Study.

    abstract::Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Dazzan P,Lawrence AJ,Reinders AATS,Egerton A,van Haren NEM,Merritt K,Barker GJ,Perez-Iglesias R,Sendt KV,Demjaha A,Nam KW,Sommer IE,Pantelis C,Wolfgang Fleischhacker W,van Rossum IW,Galderisi S,Mucci A,Drake R,Lewis S

    更新日期:2020-10-15 00:00:00

  • Sexual trauma increases the risk of developing psychosis in an ultra high-risk "prodromal" population.

    abstract::Studies indicate a high prevalence of childhood trauma in patient cohorts with established psychotic disorder and in those at risk of developing psychosis. A causal link between childhood trauma and development of psychosis has been proposed. We aimed to examine the association between experience of childhood trauma a...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Thompson AD,Nelson B,Yuen HP,Lin A,Amminger GP,McGorry PD,Wood SJ,Yung AR

    更新日期:2014-05-01 00:00:00

  • Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

    abstract::Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The curre...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Chang WC,Wong CSM,Chen EYH,Lam LCW,Chan WC,Ng RMK,Hung SF,Cheung EFC,Sham PC,Chiu HFK,Lam M,Lee EHM,Chiang TP,Chan LK,Lau GKW,Lee ATC,Leung GTY,Leung JSY,Lau JTF,van Os J,Lewis G,Bebbington P

    更新日期:2017-10-21 00:00:00

  • The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis.

    abstract::Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depres...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Upthegrove R,Lalousis P,Mallikarjun P,Chisholm K,Griffiths SL,Iqbal M,Pelton M,Reniers R,Stainton A,Rosen M,Ruef A,Dwyer DB,Surman M,Haidl T,Penzel N,Kambeitz-Llankovic L,Bertolino A,Brambilla P,Borgwardt S,Kambeitz

    更新日期:2021-01-23 00:00:00

  • Comorbid Major Depressive Disorder in Schizophrenia: A Systematic Review and Meta-Analysis.

    abstract::Comorbid major depressive disorder (MDD) in schizophrenia (SZ; SZ-MDD) has been identified as a major prognostic factor. However, the prevalence and associated factors of SZ-MDD have never been explored in a meta-analysis. All studies assessing the prevalence of SZ-MDD in stabilized outpatients with a standardized sca...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Etchecopar-Etchart D,Korchia T,Loundou A,Llorca PM,Auquier P,Lançon C,Boyer L,Fond G

    更新日期:2020-11-30 00:00:00

  • Variability and the dopamine hypothesis of schizophrenia.

    abstract::The dopamine hypothesis of schizophrenia is usually presented in a static, rather than dynamic fashion. We propose that increased dopaminergic activity may represent a stage of a dynamic schizophrenic process rather than its cause. Dopamine, as well as other neurotransmitters, responds in an adaptive fashion to stimul...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Csernansky JG,Holman CA,Hollister LE

    更新日期:1983-01-01 00:00:00

  • Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study.

    abstract:OBJECTIVE:The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores ...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,多中心研究


    authors: Smelror RE,Jørgensen KN,Lonning V,Kelleher I,Cannon M,DeRosse P,Malhotra AK,Karlsgodt KH,Andreassen OA,Lundberg M,Edbom T,Cleland N,Ueland T,Myhre AM,Rund BR,Agartz I

    更新日期:2019-06-18 00:00:00

  • Schizophrenia spectrum disorders in persons exposed to ionizing radiation as a result of the Chernobyl accident.

    abstract::We studied schizophrenia spectrum disorders in Chernobyl accident survivors by analyzing Chernobyl exclusion zone (EZ) archives (1986-1997) and by conducting a psychophysiological examination of 100 patients with acute radiation sickness (ARS) and 100 workers of the Chernobyl EZ who had worked as "liquidators-voluntee...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Loganovsky KN,Loganovskaja TK

    更新日期:2000-01-01 00:00:00

  • Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles in First-Episode Psychosis.

    abstract::Although there is recent evidence that cells from the peripheral immune system can gain access to the central nervous system in certain conditions such as multiple sclerosis, their role has not been assessed in psychosis. Here, we aimed to explore whether blood cell count was associated with brain volume and/or clinic...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Núñez C,Stephan-Otto C,Usall J,Bioque M,Lobo A,González-Pinto A,Pina-Camacho L,Vieta E,Castro-Fornieles J,Rodriguez-Jimenez R,Butjosa A,Janssen J,Cabrera B,Parellada M,Bernardo M,PEPs group.

    更新日期:2019-06-18 00:00:00

  • Social networks and mental illness in a peasant society.

    abstract::Social networks of 35 mentally ill persons were studied in Lao villages. Mental illness was associated with a decrease in size of social networks, disproportionate reliance on family, and asymmetric instrumental exchange. Nonkin "sponsors" provided assistance to those alienated from or abandoned by relatives. For thos...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Westermeyer J,Pattison EM

    更新日期:1981-01-01 00:00:00

  • Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

    abstract::Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) s...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Choi JS,Park JY,Jung MH,Jang JH,Kang DH,Jung WH,Han JY,Choi CH,Hong KS,Kwon JS

    更新日期:2012-11-01 00:00:00

  • Rationale and baseline characteristics of PREVENT: a second-generation intervention trial in subjects at-risk (prodromal) of developing first-episode psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for the prevention of psychosi

    abstract::Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Bechdolf A,Müller H,Stützer H,Wagner M,Maier W,Lautenschlager M,Heinz A,de Millas W,Janssen B,Gaebel W,Michel TM,Schneider F,Lambert M,Naber D,Brüne M,Krüger-Özgürdal S,Wobrock T,Riedel M,Klosterkötter J,PREVENT stu

    更新日期:2011-09-01 00:00:00

  • Adolescent Stress as a Driving Factor for Schizophrenia Development-A Basic Science Perspective.

    abstract::Schizophrenia has been associated with heightened stress responsivity in adolescence that precedes onset of psychosis. We now report that multiple stressors during adolescence in normal rats leads to deficits in adults analogous to that seen in schizophrenia patients. Moreover, impairment of stress control by lesion o...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Gomes FV,Grace AA

    更新日期:2017-05-01 00:00:00

  • Concurrent and predictive validity of components of disordered thinking in schizophrenia.

    abstract::Although the various manifestations of disordered thought have played a central role in diagnostic and theoretical considerations of schizophrenia, such symptoms have not been found specific to schizophrenia, and at best have shown weak relations to outcome. As part of a 7-year followup study of a sample of young, acu...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Knight RA,Elliott DS,Roff JD,Watson CG

    更新日期:1986-01-01 00:00:00

  • A selective review of recent North American long-term followup studies of schizophrenia.

    abstract::North American outcome studies of schizophrenia conducted within the past quarter century are reviewed if their minimum average followup is 10 years and they meet at least some modern design criteria. Ten such investigations are described and summarized. Taken as a whole, they demonstrate that schizophrenia can be a c...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: McGlashan TH

    更新日期:1988-01-01 00:00:00

  • Psychosis endophenotypes in schizophrenia and bipolar disorder.

    abstract::Recent studies provide considerable evidence that schizophrenia and bipolar disorder may share overlapping etiologic determinants. Identifying disease-related genetic effects is a major focus in schizophrenia and bipolar disorder research, with implications for clarifying diagnosis and developing specific treatments f...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Thaker G

    更新日期:2008-07-01 00:00:00

  • On the centrality and significance of stimulus-encoding deficit in schizophrenia.

    abstract::Increased latency of stimulus encoding is presented as a central deficit in schizophrenia cognition. Encoding, here, entails the internal representation of presenting stimuli in a format facilitating their implementation in other cognitive processes, such as those taking place in working memory. Historical roots of su...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Neufeld RW

    更新日期:2007-07-01 00:00:00

  • The genetic deconstruction of psychosis.

    abstract::Psychiatric research, including the search for predisposing genes, has tended to proceed under the assumptions that schizophrenia and bipolar disorder, as defined in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and International Statistical Classification of Diseases, 10th Revision, are discr...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Owen MJ,Craddock N,Jablensky A

    更新日期:2007-07-01 00:00:00

  • Psychotic controls in schizophrenia research.

    abstract::Schizophrenia is but one form of psychosis; therefore, it is important to control for the psychotic factor in studies of the schizophrenic syndrome. A survey was done of 478 articles in 15 major psychiatric and psychological journals to determine the frequency of controls for psychosis in schizophrenia research. The s...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Ritzler BA,Rinehart K

    更新日期:1981-01-01 00:00:00

  • Shared neurocognitive dysfunctions in young offspring at extreme risk for schizophrenia or bipolar disorder in eastern quebec multigenerational families.

    abstract:BACKGROUND:Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of famili...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Maziade M,Rouleau N,Gingras N,Boutin P,Paradis ME,Jomphe V,Boutin J,Létourneau K,Gilbert E,Lefebvre AA,Doré MC,Marino C,Battaglia M,Mérette C,Roy MA

    更新日期:2009-09-01 00:00:00

  • Prospective study of course of illness in schizophrenia: Part I. Outcome at 1 year.

    abstract::In a prospective study involving 161 patients discharged from inpatient psychiatric treatment, outcome data were obtained for 93 percent of the patients 1 year after clinic discharge. Sixty-seven percent of the patients were directly interviewed for the followup examination. Outcome data for symptomatology, relapses, ...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Pietzcker A,Gaebel W

    更新日期:1987-01-01 00:00:00

  • Long-term course of hospitalization for schizophrenia: Part II. Change with passage of time.

    abstract::This analysis examines the notion of progressive deterioration in schizophrenia, using long-term followup data on hospital episodes in defined cohorts from psychiatric case registers in Victoria, Australia; Denmark; and Salford, England. The analyses differentiate heterogeneity existing at the first hospitalization fo...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Eaton WW,Bilker W,Haro JM,Herrman H,Mortensen PB,Freeman H,Burgess P

    更新日期:1992-01-01 00:00:00

  • Schizophrenia Spectrum Disorders in a Danish 22q11.2 Deletion Syndrome Cohort Compared to the Total Danish Population--A Nationwide Register Study.

    abstract:OBJECTIVE:Cross-sectional studies have shown associations between 22q11.2 deletion syndrome and schizophrenia. However, large-scale prospective studies have been lacking. We, therefore, conducted the first large-scale population based study on the risk of being diagnosed with schizophrenia in persons identified with 22...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Vangkilde A,Olsen L,Hoeffding LK,Pedersen CB,Mortensen PB,Werge T,Trabjerg B

    更新日期:2016-05-01 00:00:00

  • A Network Approach to Psychosis: Pathways Between Childhood Trauma and Psychotic Symptoms.

    abstract::Childhood trauma (CT) has been identified as a potential risk factor for the onset of psychotic disorders. However, to date, there is limited consensus with respect to which symptoms may ensue after exposure to trauma in early life, and whether specific pathways may account for these associations. The aim of the prese...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: Isvoranu AM,van Borkulo CD,Boyette LL,Wigman JT,Vinkers CH,Borsboom D,Group Investigators.

    更新日期:2017-01-01 00:00:00

  • Psychosis as a disorder of reduced cathectic capacity: Freud's analysis of the Schreber case revisited.

    abstract::Approximately 100 years ago, a prominent German public figure name Daniel Schreber wrote memoirs of his experiences in asylums. His case was diagnosed Dementia Praecox at times and Paranoia at others by his treaters. Freud analyzed Schreber's memoirs from the perspective of his "libido" theory of developmentally organ...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章


    authors: McGlashan TH

    更新日期:2009-05-01 00:00:00

  • A review of cognitive training in schizophrenia.

    abstract::Empirically supported treatments for schizophrenia now include a variety of psychosocial interventions, such as social skills training, vocational rehabilitation, and psychotherapy. As awareness of the functional importance of neurocognitive impairments in schizophrenia has increased, interest in treatments to improve...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Twamley EW,Jeste DV,Bellack AS

    更新日期:2003-01-01 00:00:00

  • Does long-term treatment of schizophrenia with antipsychotic medications facilitate recovery?

    abstract::Antipsychotic medications are viewed as cornerstones for both the short-term and long-term treatment of schizophrenia. However, evidence on long-term (10 or more years) efficacy of antipsychotics is mixed. Double-blind discontinuation studies indicate significantly more relapses in unmedicated schizophrenia patients i...

    journal_title:Schizophrenia bulletin

    pub_type: 杂志文章,评审


    authors: Harrow M,Jobe TH

    更新日期:2013-09-01 00:00:00