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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/29148569/exome-sequence-analysis-and-follow-up-genotyping-implicates-rare-ulk1-variants-to-be-involved-in-susceptibility-to-schizophrenia
#1
Mariam M Al Eissa, Alessia Fiorentino, Sally I Sharp, Niamh L O'Brien, Kate Wolfe, Giovanni Giaroli, David Curtis, Nicholas J Bass, Andrew McQuillin
Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Exome sequence data from a SCZ cas-control sample from Sweden was analysed for likely aetiological variants using a weighted burden test. Suggestive evidence implicated the UNC-51-like kinase (ULK1) gene, and it was observed that four rare variants that were more common in the Swedish SCZ cases were also more common in UK10K SCZ cases, as compared to obesity cases...
November 17, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/29078306/widespread-covariation-of-early-environmental-exposures-and-trait-associated-polygenic-variation
#2
E Krapohl, L J Hannigan, J-B Pingault, H Patel, N Kadeva, C Curtis, G Breen, S J Newhouse, T C Eley, P F O'Reilly, R Plomin
Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29065934/polygenic-risk-for-schizophrenia-transition-and-cortical-gyrification-a-high-risk-study
#3
E Neilson, C Bois, T-K Clarke, L Hall, E C Johnstone, D G C Owens, H C Whalley, A M McIntosh, S M Lawrie
BACKGROUND: Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia. METHODS: The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16)...
October 25, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/29049906/interaction-between-compound-genetic-risk-for-schizophrenia-and-high-birth-weight-contributes-to-social-anhedonia-and-schizophrenia-in-women
#4
Johanna Liuhanen, Jaana Suvisaari, Eero Kajantie, Jouko Miettunen, Antti-Pekka Sarin, Marjo-Riitta Järvelin, Jouko Lönnqvist, Juha Veijola, Tiina Paunio
Schizophrenia is a highly heritable disease, but despite extensive study, its genetic background remains unresolved. The lack of environmental measures in genetic studies may offer some explanation. In recent Finnish studies, high birth weight was found to increase the risk for familial schizophrenia. We examined the interaction between a polygenic risk score for schizophrenia and high birth weight on social anhedonia and schizophrenia in a general population birth cohort. The study sample included 4223 participants from the 1966 Northern Finland Birth Cohort...
October 9, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29040798/assessment-of-cognition-and-personality-as-potential-endophenotypes-in-the-western-australian-family-study-of-schizophrenia
#5
Nina S McCarthy, Johanna C Badcock, Melanie L Clark, Emma E M Knowles, Gemma Cadby, Phillip E Melton, Vera A Morgan, John Blangero, Eric K Moses, David C Glahn, Assen Jablensky
Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis. In this study we assess 20 cognitive and personality measures in a sample of 127 families with at least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control families (n = 121) against 4 endophenotype criteria: (a) be associated with the illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate with the illness in families, and (d) be found in unaffected relatives at a higher rate than in the general population...
October 12, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29024729/integrating-genome-wide-association-study-and-expression-quantitative-trait-locus-study-identifies-multiple-genes-and-gene-sets-associated-with-schizophrenia
#6
Yan Zhao, Awen He, Feng Zhu, Miao Ding, Jingcan Hao, Qianrui Fan, Ping Li, Li Liu, Yanan Du, Xiao Liang, Xiong Guo, Feng Zhang, Xiancang Ma
Schizophrenia is a serious mental disease with high heritability. To better understand the genetic basis of schizophrenia, we conducted a large scale integrative analysis of genome-wide association study (GWAS) and expression quantitative trait loci (eQTLs) data. GWAS summary data was derived from a published GWAS of schizophrenia, containing 9394 schizophrenia patients and 12,462 healthy controls. The eQTLs dataset was obtained from an eQTLs meta-analysis of 5311 subjects, containing 923,021 cis-eQTLs for 14,329 genes and 4732 trans-eQTLs for 2612 genes...
October 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#7
REVIEW
Ellen S Ovenden, Nathaniel W McGregor, Robin A Emsley, Louise Warnich
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes...
October 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28989979/haplotype-based-association-analysis-of-general-cognitive-ability-in-generation-scotland-the-english-longitudinal-study-of-ageing-and-uk-biobank
#8
David M Howard, Mark J Adams, Toni-Kim Clarke, Eleanor M Wigmore, Yanni Zeng, Saskia P Hagenaars, Donald M Lyall, Pippa A Thomson, Kathryn L Evans, David J Porteous, Reka Nagy, Caroline Hayward, Chris S Haley, Blair H Smith, Alison D Murray, G David Batty, Ian J Deary, Andrew M McIntosh
BACKGROUND: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. METHODS: In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28987712/heritability-of-schizophrenia-and-schizophrenia-spectrum-based-on-the-nationwide-danish-twin-register
#9
Rikke Hilker, Dorte Helenius, Birgitte Fagerlund, Axel Skytthe, Kaare Christensen, Thomas M Werge, Merete Nordentoft, Birte Glenthøj
BACKGROUND: Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology. METHODS: Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs)...
September 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28967348/psychotic-patients-who-used-cannabis-frequently-before-illness-onset-have-higher-genetic-predisposition-to-schizophrenia-than-those-who-did-not
#10
M Aas, I Melle, F Bettella, S Djurovic, S Le Hellard, T Bjella, P A Ringen, T V Lagerberg, O B Smeland, I Agartz, O A Andreassen, M Tesli
BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use...
October 2, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28936707/immunoglobulin-genotypes-and-cognitive-functions-in-schizophrenia
#11
Janardan P Pandey, Aryan M Namboodiri, Paul J Nietert, Reiji Yoshimura, Hikaru Hori
Exposure to neurotropic viruses, such as herpes simplex virus type 1 and human cytomegalovirus, has been reported to be associated with cognitive impairment in schizophrenia. These viruses have evolved highly sophisticated strategies for decreasing the efficacy of the host immune response and interfering with viral clearance. Particular immunoglobulin GM (γ marker) genotypes modulate these viral immunoevasion strategies, influence antibody responsiveness to viral proteins, and are also associated with susceptibility to schizophrenia, providing an excellent rationale for determining their possible involvement in the cognitive functions in this highly heritable neurodevelopmental disorder...
September 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28902459/exome-sequences-of-multiplex-multigenerational-families-reveal-schizophrenia-risk-loci-with-potential-implications-for-neurocognitive-performance
#12
Mark Z Kos, Melanie A Carless, Juan Peralta, Joanne E Curran, Ellen E Quillen, Marcio Almeida, August Blackburn, Lucy Blondell, David R Roalf, Michael F Pogue-Geile, Ruben C Gur, Harald H H Göring, Vishwajit L Nimgaonkar, Raquel E Gur, Laura Almasy
Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder...
December 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28901686/shifting-the-focus-toward-rare-variants-in-schizophrenia-to-close-the-gap-from-genotype-to-phenotype
#13
REVIEW
M Leonor Bustamante, Luisa Herrera, Pablo A Gaspar, Rodrigo Nieto, Alejandro Maturana, María José Villar, Valeria Salinas, Hernán Silva
Schizophrenia (SZ) is a disorder with a high heritability and a complex architecture. Several dozen genetic variants have been identified as risk factors through genome-wide association studies including large population-based samples. However, the bulk of the risk cannot be accounted for by the genes associated to date. Rare mutations have been historically seen as relevant only for some infrequent, Mendelian forms of psychosis. Recent findings, however, show that the subset of patients that present a mutation with major effect is larger than expected...
October 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28868239/is-the-association-between-offspring-intelligence-and-parents-educational-attainment-influenced-by-schizophrenia-or-mood-disorder-in-parents
#14
Aja Neergaard Greve, Ole Mors, Erik Lykke Mortensen, Sandra Melanie Meier, John J McGrath, Liselotte Petersen
Results from twin, family, and adoption studies all suggest that general intelligence is highly heritable. Several studies have shown lower premorbid intelligence in individuals before the onset of both mood disorders and psychosis, as well as in children and adolescents at genetic high risk for developing schizophrenia. Based on these findings, we aim to investigate if the association between educational achievement in parents and intelligence in their offspring is influenced by schizophrenia or mood disorder in parents...
September 2017: Schizophrenia Research. Cognition
https://www.readbyqxmd.com/read/28855605/attempts-to-replicate-genetic-associations-with-schizophrenia-in-a-cohort-from-north-india
#15
Suman Prasad, Triptish Bhatia, Prachi Kukshal, Vishwajit L Nimgaonkar, Smita N Deshpande, B K Thelma
Schizophrenia is a chronic, severe, heritable disorder. Genome-wide association studies, conducted predominantly among Caucasians, have indicated > 100 risk alleles, with most significant SNPs on chromosome 6. There is growing interest as to whether these risk alleles are relevant in other ethnic groups as well. Neither an Indian genome-wide association studies nor a systematic replication of GWAS findings from other populations are reported. Thus, we analyzed 32 SNPs, including those associated in the Caucasian ancestry GWAS and other candidate gene studies, in a north Indian schizophrenia cohort (n = 1009 patients; n = 1029 controls) using a Sequenom mass array...
August 30, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28822116/interactions-between-variation-in-candidate-genes-and-environmental-factors-in-the-etiology-of-schizophrenia-and-bipolar-disorder-a-systematic-review
#16
REVIEW
Błażej Misiak, Filip Stramecki, Łukasz Gawęda, Katarzyna Prochwicz, Maria M Sąsiadek, Ahmed A Moustafa, Dorota Frydecka
Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28758643/complement-gene-expression-correlates-with-superior-frontal-cortical-thickness-in-humans
#17
Dana M Allswede, Amanda B Zheutlin, Yoonho Chung, Kevin Anderson, Christina M Hultman, Martin Ingvar, Tyrone D Cannon
Recent work suggest that genes encoding complement proteins that are active in the innate immune system may confer risk for schizophrenia by disrupting typical synaptic pruning in late adolescence. Alterations in the complement pathway may contribute to aberrant cortical thinning in schizophrenia prodromes and reduced prefrontal cortical thickness in chronic schizophrenia patients; however, this theory needs to be translated to humans. We conducted a series of analyses in a sample of adult Swedish twins enriched for schizophrenia (N=129) to assess the plausibility of a relationship between complement gene expression and cortical thickness that could go awry in the etiology of schizophrenia...
July 31, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28756110/a-comparative-meta-analysis-of-neurocognition-in-first-degree-relatives-of-patients-with-schizophrenia-and-bipolar-disorder
#18
E Bora
OBJECTIVE: Cognitive impairment is a familial and heritable aspect of major psychoses and might be a shared vulnerability marker for schizophrenia and BP. However, it is not clear whether some aspects of cognitive deficits are uniquely associated with risk for specific diagnoses. METHODS: A novel meta-analysis of cognitive functions in first-degree relatives of probands with bipolar disorder (BP-Rel) and schizophrenia (Sch-Rel) was conducted. Current meta-analysis included 20 studies and compared cognitive functions of 1341 Sch-Rel, 939 BP-Rel and 1427 healthy controls...
September 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28732798/the-effect-of-antipsychotic-medications-on-acoustic-startle-latency-in-schizophrenia
#19
Molly Fargotstein, Wendy Hasenkamp, Robin Gross, Bruce Cuthbert, Amanda Green, Lisette Swails, Barbara Lewison, William Boshoven, Megan Keyes, Erica Duncan
Prepulse inhibition of the acoustic startle reflex (PPI) is extensively studied as a biomarker of schizophrenia (SCZ); however, antipsychotic medication can confound the measure. Latency, the time between the startling stimulus and the reflexive eye blink, provides an index of neural processing speed and is 90% heritable. SCZ subjects have slower latency than controls (CON). This study examined the effects of antipsychotic medication on startle latency. 108 CON and 132 SCZ subjects in three medication subgroups (94 on second-generation antipsychotics (SGA), 25 on first-generation antipsychotics (FGA), 13 unmedicated (NoMed)) were tested on a standard acoustic startle paradigm designed to measure startle magnitude, PPI, and latency...
July 18, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28729842/a-gene-based-analysis-of-acoustic-startle-latency
#20
Alicia K Smith, Tanja Jovanovic, Varun Kilaru, Adriana Lori, Lauren Gensler, Samuel S Lee, Seth Davin Norrholm, Nicholas Massa, Bruce Cuthbert, Bekh Bradley, Kerry J Ressler, Erica Duncan
Latency of the acoustic startle response is the time required from the presentation of startling auditory stimulus until the startle response is elicited and provides an index of neural processing speed. Latency is prolonged in subjects with schizophrenia compared to controls in some but not all studies and is 68-90% heritable in baseline startle trials. In order to determine the genetic association with latency as a potential inroad into genetically based vulnerability to psychosis, we conducted a gene-based study of latency followed by an independent replication study of significant gene findings with a single-nucleotide polymorphism (SNP)-based analysis of schizophrenia and control subjects...
2017: Frontiers in Psychiatry
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