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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28220043/partitioning-heritability-analysis-reveals-a-shared-genetic-basis-of-brain-anatomy-and-schizophrenia
#1
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
#2
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
#3
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
#4
Heather A Bruce, Peter Kochunov, Sara A Paciga, Craig L Hyde, Xing Chen, Zhiyong Xie, Baohong Zhang, Hualin S Xi, Patricio O'Donnell, Christopher Whelan, Christian R Schubert, Alfredo Bellon, Seth A Ament, Dinesh K Shukla, Xiaoming Du, Laura M Rowland, Hugh O'Neill, L Elliot 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
December 19, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27993229/development-of-two-dimensional-measures-of-restricted-and-repetitive-behavior-in-parents-and-children
#14
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
https://www.readbyqxmd.com/read/27992416/genome-wide-association-analyses-of-sleep-disturbance-traits-identify-new-loci-and-highlight-shared-genetics-with-neuropsychiatric-and-metabolic-traits
#15
Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, Andrew Loudon, Frank A J L Scheer, Shaun M Purcell, Simon D Kyle, Deborah A Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter, Richa Saxena
Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586)...
December 19, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27968732/genetics-of-schizophrenia-historical-insights-and-prevailing-evidence
#16
J van de Leemput, J L Hess, S J Glatt, M T Tsuang
Schizophrenia's (SZ's) heritability and familial transmission have been known for several decades; however, despite the clear evidence for a genetic component, it has been very difficult to pinpoint specific causative genes. Even so genetic studies have taught us a lot, even in the pregenomic era, about the molecular underpinnings and disease-relevant pathways. Recurring themes emerged revealing the involvement of neurodevelopmental processes, glutamate regulation, and immune system differential activation in SZ etiology...
2016: Advances in Genetics
https://www.readbyqxmd.com/read/27931915/stratifying-empiric-risk-of-schizophrenia-among-first-degree-relatives-using-multiple-predictors-in-two-independent-indian-samples
#17
Triptish Bhatia, Elizabeth A Gettig, Irving I Gottesman, Jonathan Berliner, N N Mishra, Vishwajit L Nimgaonkar, Smita N Deshpande
BACKGROUND: Schizophrenia (SZ) has an estimated heritability of 64-88%, with the higher values based on twin studies. Conventionally, family history of psychosis is the best individual-level predictor of risk, but reliable risk estimates are unavailable for Indian populations. Genetic, environmental, and epigenetic factors are equally important and should be considered when predicting risk in 'at risk' individuals. OBJECTIVE: To estimate risk based on an Indian schizophrenia participant's family history combined with selected demographic factors...
December 2016: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/27922606/otto-a-new-strategy-to-extract-mental-disease-relevant-combinations-of-gwas-hits-from-individuals
#18
H Ehrenreich, M Mitjans, S Van der Auwera, T P Centeno, M Begemann, H J Grabe, S Bonn, K-A Nave
Despite high heritability of schizophrenia, genome-wide association studies (GWAS) have not yet revealed distinct combinations of single-nucleotide polymorphisms (SNPs), relevant for mental disease-related, quantifiable behavioral phenotypes. Here we propose an individual-based model to use genome-wide significant markers for extracting first genetic signatures of such behavioral continua. 'OTTO' (old Germanic=heritage) marks an individual characterized by a prominent phenotype and a particular load of phenotype-associated risk SNPs derived from GWAS that likely contributed to the development of his personal mental illness...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27916686/altered-cytokine-profile-pain-sensitivity-and-stress-responsivity-in-mice-with-co-disruption-of-the-developmental-genes-neuregulin-1%C3%A3-disc1
#19
Lieve Desbonnet, Rachel Cox, Orna Tighe, Donna Lai, Richard P Harvey, John L Waddington, Colm M P O'Tuathaigh
The complex genetic origins of many human disorders suggest that epistatic (gene×gene) interactions may contribute to a significant proportion of their heritability estimates and phenotypic heterogeneity. Simultaneous disruption of the developmental genes and schizophrenia risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) in mice has been shown to produce disease-relevant and domain-specific phenotypic profiles different from that observed following disruption of either gene alone. In the current study, anxiety and stress responsivity phenotypes in male and female mutant mice with simultaneous disruption of DISC1 and NRG1 were examined...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27872268/consistent-functional-connectivity-alterations-in-schizophrenia-spectrum-disorder-a-multisite-study
#20
Kristina C Skåtun, Tobias Kaufmann, Nhat Trung Doan, Dag Alnæs, Aldo Córdova-Palomera, Erik G Jönsson, Helena Fatouros-Bergman, Lena Flyckt, Ingrid Melle, Ole A Andreassen, Ingrid Agartz, Lars T Westlye
Schizophrenia (SZ) is a severe mental illness with high heritability and complex etiology. Mounting evidence from neuroimaging has implicated disrupted brain network connectivity in the pathophysiology. However, previous findings are inconsistent, likely due to a combination of methodological and clinical variability and relatively small sample sizes. Few studies have used a data-driven approach for characterizing pathological interactions between regions in the whole brain and evaluated the generalizability across independent samples...
November 21, 2016: Schizophrenia Bulletin
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