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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/29789256/systems-level-analysis-of-risk-genes-reveals-the-modular-nature-of-schizophrenia
#1
Jiewei Liu, Ming Li, Xiong-Jian Luo, Bing Su
Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent genome-wide association studies) have identified many risk genes for schizophrenia. However, the physical interactions among the proteins encoded by schizophrenia risk genes remain elusive and it is not known whether the identified risk genes converge on common molecular networks or pathways. Here we systematically investigated the network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions (PPI) from the human interactome...
May 19, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29765027/polygenic-pleiotropy-and-potential-causal-relationships-between-educational-attainment-neurobiological-profile-and-positive-psychotic-symptoms
#2
Yen-Feng Lin, Chia-Yen Chen, Dost Öngür, Rebecca Betensky, Jordan W Smoller, Deborah Blacker, Mei-Hua Hall
Event-related potential (ERP) components have been used to assess cognitive functions in patients with psychotic illness. Evidence suggests that among patients with psychosis there is a distinct heritable neurophysiologic phenotypic subtype captured by impairments across a range of ERP measures. In this study, we investigated the genetic basis of this "globally impaired" ERP cluster and its relationship to psychosis and cognitive abilities. We applied K-means clustering to six ERP measures to re-derive the globally impaired (n = 60) and the non-globally impaired ERP clusters (n = 323) in a sample of cases with schizophrenia (SCZ = 136) or bipolar disorder (BPD = 121) and healthy controls (n = 126)...
May 16, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29741616/a-systematic-review-of-genome-wide-research-on-psychotic-experiences-and-negative-symptom-traits-new-revelations-and-implications-for-psychiatry
#3
Angelica Ronald, Oliver Pain
We present a systematic review of genome-wide research on psychotic experience and negative symptom traits (PENS) in the community. We integrate these new findings, most of which have emerged over the last four years, with more established behaviour genetic and epidemiological research. The review includes the first genome-wide association studies of PENS, including a recent meta-analysis, and the first SNP heritability estimates. Sample sizes of < 10,000 participants mean that no genome-wide significant variants have yet been replicated...
May 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29740596/neuregulin-1-type-i-overexpression-is-associated-with-reduced-nmda-receptor-mediated-synaptic-signaling-in-hippocampal-interneurons-expressing-pv-or-cck
#4
Dimitrios Kotzadimitriou, Wiebke Nissen, Melinda Paizs, Kathryn Newton, Paul J Harrison, Ole Paulsen, Karri Lamsa
Hypofunction of N -methyl-d-aspartate receptors (NMDARs) in inhibitory GABAergic interneurons is implicated in the pathophysiology of schizophrenia (SZ), a heritable disorder with many susceptibility genes. However, it is still unclear how SZ risk genes interfere with NMDAR-mediated synaptic transmission in diverse inhibitory interneuron populations. One putative risk gene is neuregulin 1 ( NRG1 ), which signals via the receptor tyrosine kinase ErbB4, itself a schizophrenia risk gene. The type I isoform of NRG1 shows increased expression in the brain of SZ patients, and ErbB4 is enriched in GABAergic interneurons expressing parvalbumin (PV) or cholecystokinin (CCK)...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29739866/region-specific-regulation-of-presynaptic-dopamine-homeostasis-by-d2-autoreceptors-shapes-the-in-vivo-impact-of-the-neuropsychiatric-disease-associated-dat-variant-val559
#5
Raajaram Gowrishankar, Paul J Gresch, Gwynne L Davis, Rania M Katamish, Justin R Riele, Adele M Stewart, Roxanne A Vaughan, Maureen K Hahn, Randy D Blakely
Disruptions of dopamine (DA) signaling contribute to a broad spectrum of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), addiction, bipolar disorder and schizophrenia. Despite evidence that risk for these disorders derives from heritable variation in DA-linked genes, a better understanding is needed of the molecular and circuit context through which gene variation drives distinct disease traits. Previously, we identified the DA transporter (DAT) variant Val559 in subjects with ADHD and established that the mutation supports anomalous DAT-mediated DA efflux (ADE)...
May 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29728367/integration-of-enhancer-promoter-interactions-with-gwas-summary-results-identifies-novel-schizophrenia-associated-genes-and-pathways
#6
Chong Wu, Wei Pan
It remains challenging to boost statistical power of GWAS to identify more risk variants or loci that can account for "missing heritability". Furthermore, since most identified variants are not in gene coding regions, a biological interpretation of their function largely lacks. On the other hand, recent biotechnological advances have made it feasible to experimentally measure the three-dimensional organization of the genome, including enhancer-promoter interactions in high resolutions. Due to the well known critical roles of enhancer-promoter interactions in regulating gene expression programs, such data have been applied to link GWAS risk variants to their putative target genes, gaining insights into underlying biological mechanisms...
May 4, 2018: Genetics
https://www.readbyqxmd.com/read/29720671/genetic-variation-in-117-myelination-related-genes-in-schizophrenia-replication-of-association-to-lipid-biosynthesis-genes
#7
Tomasz Stokowy, Tatiana Polushina, Ida E Sønderby, Robert Karlsson, Sudheer Giddaluru, Stephanie Le Hellard, Sarah E Bergen, Patrick F Sullivan, Ole A Andreassen, Srdjan Djurovic, Christina M Hultman, Vidar M Steen
Schizophrenia is a serious psychotic disorder with high heritability. Several common genetic variants, rare copy number variants and ultra-rare gene-disrupting mutations have been linked to disease susceptibility, but there is still a large gap between the estimated and explained heritability. Since several studies have indicated brain myelination abnormalities in schizophrenia, we aimed to examine whether variants in myelination-related genes could be associated with risk for schizophrenia. We established a set of 117 myelination genes by database searches and manual curation...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29704319/a-molecule-based-genetic-association-approach-implicates-a-range-of-voltage-gated-calcium-channels-associated-with-schizophrenia
#8
Wen Li, Chun Chieh Fan, Tuomo Mäki-Marttunen, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Srdjan Djurovic, Anders M Dale, Ole A Andreassen, Yunpeng Wang
Traditional genome-wide association studies (GWAS) have successfully detected genetic variants associated with schizophrenia. However, only a small fraction of heritability can be explained. Gene-set/pathway-based methods can overcome limitations arising from single nucleotide polymorphism (SNP)-based analysis, but most of them place constraints on size which may exclude highly specific and functional sets, like macromolecules. Voltage-gated calcium (Cav ) channels, belonging to macromolecules, are composed of several subunits whose encoding genes are located far away or even on different chromosomes...
April 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/29603866/genome-wide-analysis-of-adolescent-psychotic-like-experiences-shows-genetic-overlap-with-psychiatric-disorders
#9
Oliver Pain, Frank Dudbridge, Alastair G Cardno, Daniel Freeman, Yi Lu, Sebastian Lundstrom, Paul Lichtenstein, Angelica Ronald
This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl...
March 31, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/29573219/predicting-loneliness-with-polygenic-scores-of-social-psychological-and-psychiatric-traits
#10
A Abdellaoui, M G Nivard, J-J Hottenga, I Fedko, K J H Verweij, B M L Baselmans, E A Ehli, G E Davies, M Bartels, D I Boomsma, J T Cacioppo
Loneliness is a heritable trait that accompanies multiple disorders. The association between loneliness and mental health indices may partly be due to inherited biological factors. We constructed polygenic scores for 27 traits related to behavior, cognition and mental health and tested their prediction for self-reported loneliness in a population-based sample of 8798 Dutch individuals. Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar disorder were significantly associated with loneliness...
March 23, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29567402/suspiciousness-in-young-minds-convergent-evidence-from-non-clinical-clinical-and-community-twin-samples
#11
Han-Yu Zhou, Keri Ka-Yee Wong, Li-Juan Shi, Xi-Long Cui, Yun Qian, Wen-Qing Jiang, Ya-Song Du, Simon S Y Lui, Xue-Rong Luo, Zheng-Hui Yi, Eric F C Cheung, Anna R Docherty, Raymond C K Chan
BACKGROUND: We validated the Social Mistrust Scale (SMS) and utilized it to examine the structure, prevalence, and heritability of social mistrust in a large sample of Chinese children and adolescents. METHODS: In Study 1, a large sample of healthy twins (N=2094) aged 8 to 14years (M=10.27years, SD=2) completed the SMS. Structural equation modeling (SEM) was conducted to assess the structure of the SMS and to estimate the heritability of social mistrust in a sub-sample of twins (n=756 pairs)...
March 19, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29559372/a-double-dissociation-between-two-psychotic-phenotypes-periodic-catatonia-and-cataphasia
#12
Foucher Jack René, Zhang Yi Fan, Roser Mathilde, Lamy Julien, De Sousa Paulo Loureiro, Weibel Sébastien, Vidailhet Pierre, Mainberger Olivier, Berna Fabrice
Schizophrenia as a single liability model was confronted to the multiple psychotic phenotypes model proposed by the Wernicke-Kleist-Leonhard school, focusing on two: periodic catatonia (PC) and cataphasia (C). Both are stable and heritable psychotic phenotypes with no crossed liability and are coming with the buildup of specific residual symptoms: impairment of psychomotricity for PC and a specific disorganization of thought and language in C. Regional cerebral blood flow (rCBF) was used as a biomarker. We attempted to refute the single phenotype model by looking at relevant and specific rCBF anomalies for PC and C, that would exceed anomalies in common relative to controls (CTR), i...
March 17, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29555509/the-engineered-%C3%AE-lactoglobulin-with-complementarity-to-the-chlorpromazine-chiral-conformers
#13
Joanna I Loch, Piotr Bonarek, Magdalena Tworzydło, Ilona Łazińska, Joanna Szydłowska, Joanna Lipowska, Katarzyna Rzęsikowska, Krzysztof Lewiński
Chlorpromazine (CPZ) is a phenothiazine acting as dopamine antagonist. Aside from application in schizophrenia therapy, chlorpromazine is found to be a putative inhibitor of proteins involved in cancers, heritable autism disorder and prion diseases. Four new β-lactoglobulin variants with double or triple substitutions: I56F/L39A, F105L/L39A, I56F/L39A/M107F or F105L/L39A/M107F changing the shape of the binding pocket were produced and their chlorpromazine binding properties have been investigated by X-ray crystallography, circular dichroism, isothermal titration calorimetry and thermophoresis...
July 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29541150/genetic-variants-involved-in-bipolar-disorder-a-rough-road-ahead
#14
Germano Orrù, Mauro Giovanni Carta
Background: Bipolar Disorder (BD), along with depression and schizophrenia, is one of the most serious mental illnesses, and one of the top 20 causes of severe impairment in everyday life. Recent molecular studies, using both traditional approaches and new procedures such as Whole-Genome Sequencing (WGS), have suggested that genetic factors could significantly contribute to the development of BD, with heritability estimates of up to 85%. However, it is assumed that BD is a multigenic and multifactorial illness with environmental factors that strongly contribute to disease development/progression, which means that progress in genetic knowledge of BD might be difficult to interpret in clinical practice...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
https://www.readbyqxmd.com/read/29528675/cognition-and-community-functioning-in-schizophrenia-the-nature-of-the-relationship
#15
Susan S Kuo, Laura Almasy, Ruben C Gur, Konasale Prasad, David R Roalf, Raquel E Gur, Vishwajit L Nimgaonkar, Michael F Pogue-Geile
Although cognition is one of the most important predictors of community functioning in schizophrenia, little is known about the causes of this correlation. To our knowledge, this study is the first to examine the extent to which this correlation is genetically mediated and whether the genetic correlation is specific to schizophrenia. Six hundred thirty-six participants from 43 multigenerational families with at least two relatives with schizophrenia and 135 unrelated controls underwent diagnostic interview and cognition and functioning assessment...
February 2018: Journal of Abnormal Psychology
https://www.readbyqxmd.com/read/29527006/genome-wide-analyses-of-self-reported-empathy-correlations-with-autism-schizophrenia-and-anorexia-nervosa
#16
Varun Warrier, Roberto Toro, Bhismadev Chakrabarti, Anders D Børglum, Jakob Grove, David A Hinds, Thomas Bourgeron, Simon Baron-Cohen
Empathy is the ability to recognize and respond to the emotional states of other individuals. It is an important psychological process that facilitates navigating social interactions and maintaining relationships, which are important for well-being. Several psychological studies have identified difficulties in both self-report and performance-based measures of empathy in a range of psychiatric conditions. To date, no study has systematically investigated the genetic architecture of empathy using genome-wide association studies (GWAS)...
March 12, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29523830/re-assessment-of-multiple-testing-strategies-for-more-efficient-genome-wide-association-studies
#17
Takahiro Otani, Hisashi Noma, Jo Nishino, Shigeyuki Matsui
Although enormous costs have been dedicated to discovering relevant disease-related genetic variants, especially in genome-wide association studies (GWASs), only a small fraction of estimated heritability can be explained by these results. This is the so-called missing heritability problem. The conventional use of overly conservative multiple testing strategies based on controlling the familywise error rate (FWER), in particular with a genome-wide significance threshold of P <5 × 10-8 , is one of the most important issues from a statistical perspective...
March 9, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29477586/evidence-for-association-between-familial-bipolar-risk-and-ventral-striatal-volume
#18
T M Lancaster
BACKGROUND: Recent genome-wide association studies (GWAS) of striatal volumes and bipolar disorder (BD) indicate these traits are heritable and share common genetic architecture, however little independent work has been conducted to help establish this relationship. METHODS: Subcortical volumes (mm3 ) of young, healthy offspring of BD (N= 32) and major depressive disorder (MDD) patients (N= 158) were compared to larger healthy control sample (NRANGE = 925-1052) adjusting for potential confounds, using data from the latest release (S1200) of the Human Connectome Project...
May 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29472613/genetic-contribution-to-theory-of-mind-in-adolescence
#19
Varun Warrier, Simon Baron-Cohen
Difficulties in 'theory of mind' (the ability to attribute mental states to oneself or others, and to make predictions about another's behaviour based on these attributions) have been observed in several psychiatric conditions. We investigate the genetic architecture of theory of mind in 4,577 13-year-olds who completed the Emotional Triangles Task (Triangles Task), a first-order test of theory of mind. We observe a small but significant female-advantage on the Triangles Task (Cohen's d = 0.19, P < 0...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29465570/transmissibility-and-familiality-of-neo-personality-dimensions-in-a-sample-of-korean-families-with-schizophrenia
#20
Soo Yeon Kim, Byung Dae Lee, Je Min Park, Young Min Lee, Eunsoo Moon, Hee Jeong Jeong, Young In Chung
Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of Neuroticism-Extraversion-Openness to experience (NEO) personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD).We have recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We have used NEO questionnaires for measuring personality and symptomatic dimensions...
February 2018: Medicine (Baltimore)
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