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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/28072414/evidence-for-genetic-heterogeneity-between-clinical-subtypes-of-bipolar-disorder
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27872260/familial-aggregation-and-heritability-of-schizophrenia-and-co-aggregation-of-psychiatric-illnesses-in-affected-families
#12
I-Jun Chou, Chang-Fu Kuo, Yu-Shu Huang, Matthew J Grainge, Ana M Valdes, Lai-Chu See, Kuang-Hui Yu, Shue-Fen Luo, Lu-Shuang Huang, Wen-Yi Tseng, Weiya Zhang, Michael Doherty
Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013...
November 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27872257/heritability-of-neuropsychological-measures-in-schizophrenia-and-nonpsychiatric-populations-a-systematic-review-and-meta-analysis
#13
Gabriëlla A M Blokland, Raquelle I Mesholam-Gately, Timothea Toulopoulou, Elisabetta C Del Re, Max Lam, Lynn E DeLisi, Gary Donohoe, James T R Walters, Larry J Seidman, Tracey L Petryshen
Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size...
November 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27867941/familial-influences-on-mismatch-negativity-and-its-association-with-plasma-glutamate-level-a-magnetoencephalographic-study-in-twins
#14
Yukika Nishimura, Yuki Kawakubo, Motomu Suga, Kenji Hashimoto, Yuichi Takei, Kunio Takei, Hideyuki Inoue, Masato Yumoto, Ryu Takizawa, Kiyoto Kasai
Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27864402/molecular-genetic-contributions-to-self-rated-health
#15
Sarah E Harris, Saskia P Hagenaars, Gail Davies, W David Hill, David C M Liewald, Stuart J Ritchie, Riccardo E Marioni, Cathie L M Sudlow, Joanna M Wardlaw, Andrew M McIntosh, Catharine R Gale, Ian J Deary
BACKGROUND: Poorer self-rated health (SRH) predicts worse health outcomes, even when adjusted for objective measures of disease at time of rating. Twin studies indicate SRH has a heritability of up to 60% and that its genetic architecture may overlap with that of personality and cognition. METHODS: We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were used to estimate the proportion of variance explained by all common autosomal single nucleotide polymorphisms (SNPs) for SRH...
November 17, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/27863252/the-allelic-landscape-of-human-blood-cell-trait-variation-and-links-to-common-complex-disease
#16
William J Astle, Heather Elding, Tao Jiang, Dave Allen, Dace Ruklisa, Alice L Mann, Daniel Mead, Heleen Bouman, Fernando Riveros-Mckay, Myrto A Kostadima, John J Lambourne, Suthesh Sivapalaratnam, Kate Downes, Kousik Kundu, Lorenzo Bomba, Kim Berentsen, John R Bradley, Louise C Daugherty, Olivier Delaneau, Kathleen Freson, Stephen F Garner, Luigi Grassi, Jose Guerrero, Matthias Haimel, Eva M Janssen-Megens, Anita Kaan, Mihir Kamat, Bowon Kim, Amit Mandoli, Jonathan Marchini, Joost H A Martens, Stuart Meacham, Karyn Megy, Jared O'Connell, Romina Petersen, Nilofar Sharifi, Simon M Sheard, James R Staley, Salih Tuna, Martijn van der Ent, Klaudia Walter, Shuang-Yin Wang, Eleanor Wheeler, Steven P Wilder, Valentina Iotchkova, Carmel Moore, Jennifer Sambrook, Hendrik G Stunnenberg, Emanuele Di Angelantonio, Stephen Kaptoge, Taco W Kuijpers, Enrique Carrillo-de-Santa-Pau, David Juan, Daniel Rico, Alfonso Valencia, Lu Chen, Bing Ge, Louella Vasquez, Tony Kwan, Diego Garrido-Martín, Stephen Watt, Ying Yang, Roderic Guigo, Stephan Beck, Dirk S Paul, Tomi Pastinen, David Bujold, Guillaume Bourque, Mattia Frontini, John Danesh, David J Roberts, Willem H Ouwehand, Adam S Butterworth, Nicole Soranzo
Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27818178/molecular-genetic-contributions-to-social-deprivation-and-household-income-in-uk-biobank
#17
W David Hill, Saskia P Hagenaars, Riccardo E Marioni, Sarah E Harris, David C M Liewald, Gail Davies, Aysu Okbay, Andrew M McIntosh, Catharine R Gale, Ian J Deary
Individuals with lower socio-economic status (SES) are at increased risk of physical and mental illnesses and tend to die at an earlier age [1-3]. Explanations for the association between SES and health typically focus on factors that are environmental in origin [4]. However, common SNPs have been found collectively to explain around 18% of the phenotypic variance of an area-based social deprivation measure of SES [5]. Molecular genetic studies have also shown that common physical and psychiatric diseases are partly heritable [6]...
November 21, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27777633/uncovering-obsessive-compulsive-disorder-risk-genes-in-a-pediatric-cohort-by-high-resolution-analysis-of-copy-number-variation
#18
Matthew J Gazzellone, Mehdi Zarrei, Christie L Burton, Susan Walker, Mohammed Uddin, S M Shaheen, Julie Coste, Rageen Rajendram, Reva J Schachter, Marlena Colasanto, Gregory L Hanna, David R Rosenberg, Noam Soreni, Kate D Fitzgerald, Christian R Marshall, Janet A Buchanan, Daniele Merico, Paul D Arnold, Stephen W Scherer
BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0...
2016: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/27762073/cognitive-analysis-of-schizophrenia-risk-genes-that-function-as-epigenetic-regulators-of-gene-expression
#19
Laura Whitton, Donna Cosgrove, Christopher Clarkson, Denise Harold, Kimberley Kendall, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, James Walters, Annette Hartmann, Betina Konte, Dan Rujescu, Michael Gill, Aiden Corvin, Stephen Rea, Gary Donohoe, Derek W Morris
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription...
December 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27732705/exploring-boundaries-for-the-genetic-consequences-of-assortative-mating-for-psychiatric-traits
#20
Wouter J Peyrot, Matthew R Robinson, Brenda W J H Penninx, Naomi R Wray
Importance: Considerable partner resemblances have been found for a wide range of psychiatric disorders, meaning that partners of affected individuals have an increased risk of being affected compared with partners of unaffected individuals. If this resemblance is reflected in genetic similarity between partners, genetic risk is anticipated to accumulate in offspring, but these potential consequences have not been quantified and have been left implicit. Observations: The anticipated consequences of partner resemblance on prevalence and heritability of psychiatric traits in the offspring generation were modeled for disorders with varying heritabilities, population prevalence (lifetime risk), and magnitudes of partner resemblance...
November 1, 2016: JAMA Psychiatry
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