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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28645778/whole-genome-sequencing-of-monozygotic-twins-discordant-for-schizophrenia-indicates-multiple-genetic-risk-factors-for-schizophrenia
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28525603/genome-wide-association-study-of-psychosis-proneness-in-the-finnish-population
#6
Alfredo Ortega-Alonso, Jesper Ekelund, Antti-Pekka Sarin, Jouko Miettunen, Juha Veijola, Marjo-Riitta Järvelin, William Hennah
The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman's Schizotypia scales), and Schizoidia scale...
May 19, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28523550/histone-posttranslational-modifications-in-schizophrenia
#7
Elizabeth A Thomas
Schizophrenia is a complex neuropsychiatric disorder with high heritability; however, family and twin studies have indicated that environmental factors also play important roles in the etiology of disease. Environmental triggers exert their influence on behavior via epigenetic mechanisms. Epigenetic modifications, such as histone acetylation and methylation, as well as DNA methylation, can induce lasting changes in gene expression and have therefore been implicated in promoting the behavioral and neuronal behaviors that characterize this disorder...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523549/dna-methylation-in-schizophrenia
#8
Lotta-Katrin Pries, Sinan Gülöksüz, Gunter Kenis
Schizophrenia is a highly heritable psychiatric condition that displays a complex phenotype. A multitude of genetic susceptibility loci have now been identified, but these fail to explain the high heritability estimates of schizophrenia. In addition, epidemiologically relevant environmental risk factors for schizophrenia may lead to permanent changes in brain function. In conjunction with genetic liability, these environmental risk factors-likely through epigenetic mechanisms-may give rise to schizophrenia, a clinical syndrome characterized by florid psychotic symptoms and moderate to severe cognitive impairment...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28494655/significant-locus-and-metabolic-genetic-correlations-revealed-in-genome-wide-association-study-of-anorexia-nervosa
#9
Laramie Duncan, Zeynep Yilmaz, Helena Gaspar, Raymond Walters, Jackie Goldstein, Verneri Anttila, Brendan Bulik-Sullivan, Stephan Ripke, Laura Thornton, Anke Hinney, Mark Daly, Patrick F Sullivan, Eleftheria Zeggini, Gerome Breen, Cynthia M Bulik
OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts...
May 12, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28461698/genetic-risk-for-schizophrenia-and-psychosis-in-alzheimer-disease
#10
M A A DeMichele-Sweet, E A Weamer, L Klei, D T Vrana, D J Hollingshead, H J Seltman, R Sims, T Foroud, I Hernandez, S Moreno-Grau, L Tárraga, M Boada, A Ruiz, J Williams, R Mayeux, O L Lopez, E L Sibille, M I Kamboh, B Devlin, R A Sweet
Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115)...
May 2, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28442247/regional-enrichment-analyses-on-genetic-profiles-for-schizophrenia-and-bipolar-disorder
#11
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
#12
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
#13
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...
June 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28418011/more-than-25-years-of-genetic-studies-of-clozapine-induced-agranulocytosis
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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