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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28902459/exome-sequences-of-multiplex-multigenerational-families-reveal-schizophrenia-risk-loci-with-potential-implications-for-neurocognitive-performance
#1
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...
September 13, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 5, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28725167/genetic-risk-between-the-cacna1i-gene-and-schizophrenia-in-chinese-uygur-population
#10
Wei Xu, Yahui Liu, Jianhua Chen, Qingli Guo, Ke Liu, Zujia Wen, Zhaowei Zhou, Zhijian Song, Juan Zhou, Lin He, Qizhong Yi, Yongyong Shi
BACKGROUND: Schizophrenia (SCZ) is a common mental disorder with high heritability, and genetic factors play a major role in the pathogenesis. Recent researches indicated that the CACNA1I involved in calcium channels probably affect the potential pathogenesis of SCZ. RESULTS: In this study, we attempted to investigate whether the CACNA1I gene contributes the risk to SCZ in the Uighur Chinese population, and performed a case-control study involving 985 patient samples and 1218 normal controls to analyze nine SNPs within the CACNA1I gene...
2018: Hereditas
https://www.readbyqxmd.com/read/28719030/polygenic-risk-for-schizophrenia-and-neurocognitive-performance-in-patients-with-schizophrenia
#11
Shi-Heng Wang, Po-Chang Hsiao, Ling-Ling Yeh, Chih-Min Liu, Chen-Chung Liu, Tzung-Jeng Hwang, Ming H Hsieh, Yi-Ling Chien, Yi-Ting Lin, Sharon D Chandler, Stephen V Faraone, Nan Laird, Benjamin Neale, Steve A McCarroll, Stephen J Glatt, Ming T Tsuang, Hai-Gwo Hwu, Wei J Chen
Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRS) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project...
July 18, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28691507/genetic-basis-of-positive-and-negative-symptom-domains-in-schizophrenia
#12
Rose Mary Xavier, Allison Vorderstrasse
Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28686564/asperger-syndrome-and-schizophrenia-%C3%AE-eurodevelopmental-continuum-or-separated-clinical-entities
#13
Chr Anomitri, H Lazaratou
This article is an overview of the literature on Asperger's syndrome and schizophrenia and aim to discuss their similarities and differences. Eugen Bleuler who associated the terms "schizophrenia" and "autism" a century ago, viewed autism as a form of solitude of schizophrenic patients representing withdrawal from reality. Ever since, there has been confusion as to the boundaries between these conditions. Nowadays recent research, from a variety of perspectives-genomics, neurodevelopment, psychiatry, etc. has given new information on these conditions...
April 2017: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28680393/potential-value-of-genomic-copy-number-variations-in-schizophrenia
#14
REVIEW
Chuanjun Zhuo, Weihong Hou, Chongguang Lin, Lirong Hu, Jie Li
Schizophrenia is a devastating neuropsychiatric disorder affecting approximately 1% of the global population, and the disease has imposed a considerable burden on families and society. Although, the exact cause of schizophrenia remains unknown, several lines of scientific evidence have revealed that genetic variants are strongly correlated with the development and early onset of the disease. In fact, the heritability among patients suffering from schizophrenia is as high as 80%. Genomic copy number variations (CNVs) are one of the main forms of genomic variations, ubiquitously occurring in the human genome...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28651857/a-polygenic-risk-score-of-glutamatergic-snps-associated-with-schizophrenia-predicts-attentional-behavior-and-related-brain-activity-in-healthy-humans
#15
Antonio Rampino, Paolo Taurisano, Giuseppe Fanelli, Mariateresa Attrotto, Silvia Torretta, Linda Antonella Antonucci, Grazia Miccolis, Giulio Pergola, Gianluca Ursini, Giancarlo Maddalena, Raffaella Romano, Rita Masellis, Pasquale Di Carlo, Patrizia Pignataro, Giuseppe Blasi, Alessandro Bertolino
Multiple genetic variations impact on risk for schizophrenia. Recent analyses by the Psychiatric Genomics Consortium (PGC2) identified 128 SNPs genome-wide associated with the disorder. Furthermore, attention and working memory deficits are core features of schizophrenia, are heritable and have been associated with variation in glutamatergic neurotransmission. Based on this evidence, in a sample of healthy volunteers, we used SNPs associated with schizophrenia in PGC2 to construct a Polygenic-Risk-Score (PRS) reflecting the cumulative risk for schizophrenia, along with a Polygenic-Risk-Score including only SNPs related to genes implicated in glutamatergic signaling (Glu-PRS)...
June 23, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28645778/whole-genome-sequencing-of-monozygotic-twins-discordant-for-schizophrenia-indicates-multiple-genetic-risk-factors-for-schizophrenia
#16
Jinsong Tang, Yu Fan, Hong Li, Qun Xiang, Deng-Feng Zhang, Zongchang Li, Ying He, Yanhui Liao, Ya Wang, Fan He, Fengyu Zhang, Yin Yao Shugart, Chunyu Liu, Yanqing Tang, Raymond C K Chan, Chuan-Yue Wang, Yong-Gang Yao, Xiaogang Chen
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight nonsynonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p...
June 8, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28608620/genome-wide-association-study-of-facial-emotion-recognition-in-children-and-association-with-polygenic-risk-for-mental-health-disorders
#17
Jonathan R I Coleman, Kathryn J Lester, Robert Keers, Marcus R Munafò, Gerome Breen, Thalia C Eley
Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight-year-old participants (n = 4,097) from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) faces test. Genome-wide genotype data was available from the Illumina HumanHap550 Quad microarray...
June 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28607503/reproductive-fitness-and-genetic-risk-of-psychiatric-disorders-in-the-general-population
#18
Niamh Mullins, Andrés Ingason, Heather Porter, Jack Euesden, Alexandra Gillett, Sigurgeir Ólafsson, Daniel F Gudbjartsson, Cathryn M Lewis, Engilbert Sigurdsson, Evald Saemundsen, Ólafur Ó Gudmundsson, Michael L Frigge, Augustine Kong, Agnar Helgason, G Bragi Walters, Omar Gustafsson, Hreinn Stefansson, Kari Stefansson
The persistence of common, heritable psychiatric disorders that reduce reproductive fitness is an evolutionary paradox. Here, we investigate the selection pressures on sequence variants that predispose to schizophrenia, autism, bipolar disorder, major depression and attention deficit hyperactivity disorder (ADHD) using genomic data from 150,656 Icelanders, excluding those diagnosed with these psychiatric diseases. Polygenic risk of autism and ADHD is associated with number of children. Higher polygenic risk of autism is associated with fewer children and older age at first child whereas higher polygenic risk of ADHD is associated with having more children...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28552414/qki6b-mrna-levels-are-upregulated-in-schizophrenia-and-predict-gfap-expression
#19
B Farnsworth, K J Radomska, B Zimmermann, P Kettunen, E Jazin, L S Emilsson
Schizophrenia is a highly heritable disorder with a heterogeneous symptomatology. Research increasingly indicates the importance of the crucial and often overlooked glial perturbations within schizophrenia. Within this study, we examined an isoform of quaking (a gene encoding an RNA-binding protein that is exclusively expressed in glial cells), known as QKI6B, and a prototypical astrocyte marker, glial fibrillary acidic protein (GFAP), postulated to be under the regulation of QKI. The expression levels of these genes were quantified across post-mortem brain samples from 55 schizophrenic individuals, and 55 healthy controls, using real-time PCR...
May 25, 2017: Brain Research
https://www.readbyqxmd.com/read/28548194/-heritability-and-genetic-comorbidity-of-attention-deficit-disorder-with-hyperactivity
#20
REVIEW
Giannina Puddu, Paula Rothhammer, Ximena Carrasco, Francisco Aboitiz, Francisco Rothhammer
This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2...
March 2017: Revista Médica de Chile
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