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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28286248/cell-migration-in-schizophrenia-patient-derived-cells-do-not-regulate-motility-in-response-to-extracellular-matrix
#1
Jing Yang Tee, Ratneswary Sutharsan, Yongjun Fan, Alan Mackay-Sim
Schizophrenia is a highly heritable psychiatric disorder linked to a large number of risk genes. The function of these genes in disease etiology is not fully understood but pathway analyses of genomic data suggest developmental dysregulation of cellular processes such as neuronal migration and axon guidance. Previous studies of patient-derived olfactory cells show them to be more motile than control-derived cells when grown on a fibronectin substrate, motility that is dependent on focal adhesion kinase signaling...
March 9, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28285025/genetic-correlation-between-smoking-behaviors-and-schizophrenia
#2
Sarah M Hartz, Amy C Horton, Dana B Hancock, Timothy B Baker, Neil E Caporaso, Li-Shiun Chen, John E Hokanson, Sharon M Lutz, Mary L Marazita, Daniel W McNeil, Carlos N Pato, Michele T Pato, Eric O Johnson, Laura J Bierut
Nicotine dependence is highly comorbid with schizophrenia, and the etiology of the comorbidity is unknown. To determine whether there is a genetic correlation of smoking behavior with schizophrenia, genome-wide association study (GWAS) meta-analysis results from five smoking phenotypes (ever/never smoker (N=74,035), age of onset of smoking (N=28,647), cigarettes smoked per day (CPD, N=38,860), nicotine dependence (N=10,666), and current/former smoker (N=40,562)) were compared to GWAS meta-analysis results from schizophrenia (N=79,845) using linkage disequilibrium (LD) score regression...
March 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28275544/polygenic-risk-for-five-psychiatric-disorders-and-cross-disorder-and-disorder-specific-neural-connectivity-in-two-independent-populations
#3
Tianqi Wang, Xiaolong Zhang, Ang Li, Meifang Zhu, Shu Liu, Wen Qin, Jin Li, Chunshui Yu, Tianzi Jiang, Bing Liu
Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS) was computed. Two independent general populations (N = 360 and N = 323) were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28259864/-an-attempt-to-identify-22q11-2-microdeletions-in-samples-of-the-hungarian-schizophrenia-dna-bank-by-multiplex-ligation-based-probe-amplification-mlpa-literature-review-methodology-and-results
#4
Izabella Klein, Katalin Szocs, Katalin Vincze, Judit Benkovits, Szilvia Somogyi, Levente Herman, Janos M Rethelyi
Schizophrenia is a severe debilitating psychiatric disorder, with a typical onset in adolescence or early adulthood. This condition is characterized by heterogeneous symptoms (hallucinations, delusions, disorganized behaviour, affective flattening, and social isolation) and a life-time prevalence of 0.5-1.2%. In spite of the efforts to uncover the etiology of the disorder, its pathogenesis and neurobiological background are poorly understood. Given the high heritability in schizophrenia, genetic research remains an important area of focus...
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28245176/familial-and-environmental-influences-on-brain-volumes-in-twins-with-schizophrenia
#5
Marco M Picchioni, Fruhling Rijsdijk, Timothea Toulopoulou, Christopher Chaddock, James H Cole, Ulrich Ettinger, Ana Oses, Hugo Metcalfe, Robin M Murray, Philip McGuire
BACKGROUND: Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. METHODS: We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually...
March 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/28243163/drug-abuse-and-psychosis-new-insights-into-drug-induced-psychosis
#6
REVIEW
Suji Ham, Tae Kyoo Kim, Sooyoung Chung, Heh-In Im
Addictive drug use or prescribed medicine abuse can cause psychosis. Some representative symptoms frequently elicited by patients with psychosis are hallucination, anhedonia, and disrupted executive functions. These psychoses are categorized into three classifications of symptoms: positive, negative, and cognitive. The symptoms of DIP are not different from the symptoms of schizophrenia, and it is difficult to distinguish between them. Due to this ambiguity of distinction between the DIP and schizophrenia, the DIP animal model has been frequently used as the schizophrenia animal model...
February 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28220043/partitioning-heritability-analysis-reveals-a-shared-genetic-basis-of-brain-anatomy-and-schizophrenia
#7
P H Lee, J T Baker, A J Holmes, N Jahanshad, T Ge, J-Y Jung, Y Cruz, D S Manoach, D P Hibar, J Faskowitz, K L McMahon, G I de Zubicaray, N H Martin, M J Wright, D Öngür, R Buckner, J Roffman, P M Thompson, J W Smoller
No abstract text is available yet for this article.
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28195573/whole-exome-sequencing-of-individuals-from-an-isolated-population-implicates-rare-risk-variants-in-bipolar-disorder
#8
F Lescai, T D Als, Q Li, M Nyegaard, G Andorsdottir, M Biskopstø, A Hedemand, A Fiorentino, N O'Brien, A Jarram, J Liang, J Grove, J Pallesen, E Eickhardt, M Mattheisen, L Bolund, D Demontis, A G Wang, A McQuillin, O Mors, J Wang, A D Børglum
Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28194004/genetic-contributions-to-self-reported-tiredness
#9
V Deary, S P Hagenaars, S E Harris, W D Hill, G Davies, D C M Liewald, A M McIntosh, C R Gale, I J Deary
Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28188958/potassium-channel-gene-associations-with-joint-processing-speed-and-white-matter-impairments-in-schizophrenia
#10
H A Bruce, P Kochunov, S A Paciga, C L Hyde, X Chen, Z Xie, B Zhang, H S Xi, P O'Donnell, C Whelan, C R Schubert, A Bellon, S A Ament, D K Shukla, X Du, L M Rowland, H O'Neill, L E Hong
Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons...
February 11, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28186152/association-of-polygenic-risk-for-major-psychiatric-illness-with-subcortical-volumes-and-white-matter-integrity-in-uk-biobank
#11
L M Reus, X Shen, J Gibson, E Wigmore, L Ligthart, M J Adams, G Davies, S R Cox, S P Hagenaars, M E Bastin, I J Deary, H C Whalley, A M McIntosh
Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28182345/a-cross-validation-design-using-age-and-hla-alleles-for-the-assessment-of-clinical-schizophrenia-risk
#12
Song Laiyu, Zhang Lei, Xie Soufu, Xv Junting, Zhou Jie, Liu Hui
BACKGROUND: Schizophrenia (SCH) is a highly heritable disease that occurs mostly in young adults. Genetic factors usually play important roles in the onset of SCH. Human leukocyte antigen complex (HLA) genes are considered to be the important genetic predisposition factor and the genetic markers in SCH and other diseases. METHODS: To screen SCH-associated HLA alleles, alleles for HLA-DRB1 and HLA-DQB1 loci were determined using the PCR-SSP typing kit. Statistically significant differences between observed and expected frequencies of allele combinations were identified...
February 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28166306/identification-of-shared-risk-loci-and-pathways-for-bipolar-disorder-and-schizophrenia
#13
Andreas J Forstner, Julian Hecker, Andrea Hofmann, Anna Maaser, Céline S Reinbold, Thomas W Mühleisen, Markus Leber, Jana Strohmaier, Franziska Degenhardt, Jens Treutlein, Manuel Mattheisen, Johannes Schumacher, Fabian Streit, Sandra Meier, Stefan Herms, Per Hoffmann, André Lacour, Stephanie H Witt, Andreas Reif, Bertram Müller-Myhsok, Susanne Lucae, Wolfgang Maier, Markus Schwarz, Helmut Vedder, Jutta Kammerer-Ciernioch, Andrea Pfennig, Michael Bauer, Martin Hautzinger, Susanne Moebus, Lorena M Schenk, Sascha B Fischer, Sugirthan Sivalingam, Piotr M Czerski, Joanna Hauser, Jolanta Lissowska, Neonila Szeszenia-Dabrowska, Paul Brennan, James D McKay, Adam Wright, Philip B Mitchell, Janice M Fullerton, Peter R Schofield, Grant W Montgomery, Sarah E Medland, Scott D Gordon, Nicholas G Martin, Valery Krasnov, Alexander Chuchalin, Gulja Babadjanova, Galina Pantelejeva, Lilia I Abramova, Alexander S Tiganov, Alexey Polonikov, Elza Khusnutdinova, Martin Alda, Cristiana Cruceanu, Guy A Rouleau, Gustavo Turecki, Catherine Laprise, Fabio Rivas, Fermin Mayoral, Manolis Kogevinas, Maria Grigoroiu-Serbanescu, Tim Becker, Thomas G Schulze, Marcella Rietschel, Sven Cichon, Heide Fier, Markus M Nöthen
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls)...
2017: PloS One
https://www.readbyqxmd.com/read/28115742/mef2c-transcription-factor-is-associated-with-the-genetic-and-epigenetic-risk-architecture-of-schizophrenia-and-improves-cognition-in-mice
#14
A C Mitchell, B Javidfar, V Pothula, D Ibi, E Y Shen, C J Peter, L K Bicks, T Fehr, Y Jiang, K J Brennand, R L Neve, J Gonzalez-Maeso, S Akbarian
Large-scale consortia mapping the genomic risk architectures of schizophrenia provide vast amounts of molecular information, with largely unexplored therapeutic potential. We harnessed publically available information from the Psychiatric Genomics Consortium, and report myocyte enhancer factor 2C (MEF2C) motif enrichment in sequences surrounding the top scoring single-nucleotide polymorphisms within risk loci contributing by individual small effect to disease heritability. Chromatin profiling at base-pair resolution in neuronal nucleosomes extracted from prefrontal cortex of 34 subjects, including 17 cases diagnosed with schizophrenia, revealed MEF2C motif enrichment within cis-regulatory sequences, including neuron-specific promoters and superenhancers, affected by histone H3K4 hypermethylation in disease cases...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28099358/the-gender-specific-association-of-rs334558-in-gsk3%C3%AE-with-major-depressive-disorder
#15
Sha Liu, Le Wang, Ning Sun, Chunxia Yang, Zhifen Liu, Xinrong Li, Xiaohua Cao, Yong Xu, Kerang Zhang
Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent.In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28072414/evidence-for-genetic-heterogeneity-between-clinical-subtypes-of-bipolar-disorder
#16
A W Charney, D M Ruderfer, E A Stahl, J L Moran, K Chambert, R A Belliveau, L Forty, K Gordon-Smith, A Di Florio, P H Lee, E J Bromet, P F Buckley, M A Escamilla, A H Fanous, L J Fochtmann, D S Lehrer, D Malaspina, S R Marder, C P Morley, H Nicolini, D O Perkins, J J Rakofsky, M H Rapaport, H Medeiros, J L Sobell, E K Green, L Backlund, S E Bergen, A Juréus, M Schalling, P Lichtenstein, P Roussos, J A Knowles, I Jones, L A Jones, C M Hultman, R H Perlis, S M Purcell, S A McCarroll, C N Pato, M T Pato, N Craddock, M Landén, J W Smoller, P Sklar
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1)...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28039552/cerebrospinal-fluid-microglia-and-neurodegenerative-markers-in-twins-concordant-and-discordant-for-psychotic-disorders
#17
Viktoria Johansson, Joel Jakobsson, Rebecca G Fortgang, Henrik Zetterberg, Kaj Blennow, Tyrone D Cannon, Christina M Hultman, Lennart Wetterberg, Mikael Landén
Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling...
December 30, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28036406/winner-s-curse-correction-and-variable-thresholding-improve-performance-of-polygenic-risk-modeling-based-on-genome-wide-association-study-summary-level-data
#18
Jianxin Shi, Ju-Hyun Park, Jubao Duan, Sonja T Berndt, Winton Moy, Kai Yu, Lei Song, William Wheeler, Xing Hua, Debra Silverman, Montserrat Garcia-Closas, Chao Agnes Hsiung, Jonine D Figueroa, Victoria K Cortessis, Núria Malats, Margaret R Karagas, Paolo Vineis, I-Shou Chang, Dongxin Lin, Baosen Zhou, Adeline Seow, Keitaro Matsuo, Yun-Chul Hong, Neil E Caporaso, Brian Wolpin, Eric Jacobs, Gloria M Petersen, Alison P Klein, Donghui Li, Harvey Risch, Alan R Sanders, Li Hsu, Robert E Schoen, Hermann Brenner, Rachael Stolzenberg-Solomon, Pablo Gejman, Qing Lan, Nathaniel Rothman, Laufey T Amundadottir, Maria Teresa Landi, Douglas F Levinson, Stephen J Chanock, Nilanjan Chatterjee
Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27995564/a-review-of-the-functional-and-anatomical-default-mode-network-in-schizophrenia
#19
REVIEW
Mao-Lin Hu, Xiao-Fen Zong, J John Mann, Jun-Jie Zheng, Yan-Hui Liao, Zong-Chang Li, Ying He, Xiao-Gang Chen, Jin-Song Tang
Schizophrenia is a severe mental disorder characterized by impaired perception, delusions, thought disorder, abnormal emotion regulation, altered motor function, and impaired drive. The default mode network (DMN), since it was first proposed in 2001, has become a central research theme in neuropsychiatric disorders, including schizophrenia. In this review, first we define the DMN and describe its functional activity, functional and anatomical connectivity, heritability, and inverse correlation with the task positive network...
February 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27993229/development-of-two-dimensional-measures-of-restricted-and-repetitive-behavior-in-parents-and-children
#20
David W Evans, Mirko Uljarević, Laina G Lusk, Eva Loth, Thomas Frazier
OBJECTIVE: Restricted and repetitive behaviors (RRBs) are a heterogeneous set of behaviors common across a wide range of neurodevelopmental disorders (NDDs) and neuropsychiatric disorders (NPDs) that extend well into the general population. This study introduces 2 dimensional measurements of RRBs for use in typical and clinical populations from infancy to adulthood. METHOD: The Childhood Routines Inventory-Revised (CRI-R) and the Adult Routines Inventory (ARI) were created and administered online to a nationally representative cohort of 3,108 parents with 3,032 children (range 12 months to 17 years 11 months)...
January 2017: Journal of the American Academy of Child and Adolescent Psychiatry
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