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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28442247/regional-enrichment-analyses-on-genetic-profiles-for-schizophrenia-and-bipolar-disorder
#1
Jingyu Liu, Jiayu Chen, Nora I Perrone-Bizzozero, Jessica A Turner, Vince D Calhoun
Both schizophrenia (SZ) and bipolar disorder (BD) are highly heritable psychiatric disorders. The significant genomic risk loci are of great importance but with no guarantee of known functional impact and they cannot totally explain the genetic inheritance. In this study we present regional enrichment analyses across the genome, aiming to strike a balance between individual risk loci and integrated regional effects. Chromosomes were partitioned into 2 million base-pair regions (indicated by an underscore sign in the cytogenetic bands) on which enrichment tests are performed...
April 22, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28439101/largest-gwas-of-ptsd-n-20%C3%A2-070-yields-genetic-overlap-with-schizophrenia-and-sex-differences-in-heritability
#2
L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h(2)SNP) for European-American females of 29% that is similar to h(2)SNP for schizophrenia and is substantially higher than h(2)SNP in European-American males (estimate not distinguishable from zero)...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28422133/gene-set-analysis-shows-association-between-fmrp-targets-and-autism-spectrum-disorder
#3
Arija Jansen, Gwen C Dieleman, August B Smit, Matthijs Verhage, Frank C Verhulst, Tinca J C Polderman, Danielle Posthuma
Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding biological mechanisms are largely unknown. Our objective is to investigate the contribution of common genetic variation to biological pathways functionally involved in ASD. We conducted gene-set analyses to identify ASD-associated functional biological pathways using the statistical tools MAGMA and INRICH...
April 19, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28418011/more-than-25-years-of-genetic-studies-of-clozapine-induced-agranulocytosis
#4
REVIEW
S A J de With, S L Pulit, W G Staal, R S Kahn, R A Ophoff
Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical practice. The etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is thought to be a heritable trait. We reviewed the genetic studies of CIA published thus far. One recurrent finding from early candidate gene study to more recent genome-wide analysis is that of the involvement of human leukocyte antigen locus...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28398343/large-scale-interaction-effects-reveal-missing-heritability-in-schizophrenia-bipolar-disorder-and-posttraumatic-stress-disorder
#5
H J Woo, C Yu, K Kumar, J Reifman
Genetic susceptibility factors behind psychiatric disorders typically contribute small effects individually. A possible explanation for the missing heritability is that the effects of common variants are not only polygenic but also non-additive, appearing only when interactions within large groups are taken into account. Here, we tested this hypothesis for schizophrenia (SZ) and bipolar disorder (BP) disease risks, and identified genetic factors shared with posttraumatic stress disorder (PTSD). When considered independently, few single-nucleotide polymorphisms (SNPs) reached genome-wide significance...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28383650/schizotypy-independent-and-schizotypy-modulated-cognitive-impairments-in-unaffected-first-degree-relatives-of-schizophrenia-spectrum-patients
#6
Chrysoula Zouraraki, Penny Karamaouna, Leda Karagiannopoulou, Stella G Giakoumaki
Objective: The aim of the study was to compare the neurocognitive profile of unaffected first-degree relatives of schizophrenia patients with control individuals, controlling for different schizotypal traits. Method: One hundred and fifteen adult unaffected first-degree relatives of schizophrenia-spectrum patients and 122 controls were tested for schizotypy with the Schizotypal Personality Questionnaire. They also underwent a thorough neurocognitive assessment with a range of tasks covering several aspects of executive functioning...
April 5, 2017: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
https://www.readbyqxmd.com/read/28360375/the-path-to-new-therapies-for-schizophrenia-and-bipolar-illness
#7
Edward M Scolnick
Schizophrenia and bipolar illness are two of the most serious forms of mental illness. Until relatively recently, almost nothing was known about the molecular pathogenesis of either illness. The single largest risk factor that predisposes people to schizophrenia or bipolar illness is genetic risk. Heritability is high, and the incidence is significantly higher in identical twins than in nonidentical twins. Despite decades of work aimed at identifying the genes involved in these two illnesses, virtually no progress had been made until the past decade...
April 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28358316/theranostic-biomarkers-for-schizophrenia
#8
REVIEW
Matea Nikolac Perkovic, Gordana Nedic Erjavec, Dubravka Svob Strac, Suzana Uzun, Oliver Kozumplik, Nela Pivac
Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28344127/replicated-association-between-the-european-gwas-locus-rs10503253-at-csmd1-and-schizophrenia-in-asian-population
#9
Weiqing Liu, Fang Liu, Xiufeng Xu, Yan Bai
Schizophrenia is one of the most severe mental disorders with significant heritability. Recent genetic association studies including genome-wide association studies (GWAS) have identified multiple common variants conferring risk of schizophrenia. An intronic SNP within CSMD1, rs10503253, is one of the top risk SNPs for schizophrenia in Europeans discovered through large GWAS. However, whether rs10503253 is also a risk SNP for schizophrenia in other populations, such as Asians, is still unknown. To answer this question, we examined the association of rs10503253 with schizophrenia in a total of 7514 schizophrenia patients, 9058 healthy controls and 1115 nuclear families originated from Asia using a meta-analytic approach...
March 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28286248/cell-migration-in-schizophrenia-patient-derived-cells-do-not-regulate-motility-in-response-to-extracellular-matrix
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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