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Heritability of schizophrenia

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https://www.readbyqxmd.com/read/27872268/consistent-functional-connectivity-alterations-in-schizophrenia-spectrum-disorder-a-multisite-study
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27725659/rare-deleterious-mutations-are-associated-with-disease-in-bipolar-disorder-families
#11
A R Rao, M Yourshaw, B Christensen, S F Nelson, B Kerner
Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction...
October 11, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27725656/partitioning-heritability-analysis-reveals-a-shared-genetic-basis-of-brain-anatomy-and-schizophrenia
#12
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
Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals...
December 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27683010/the-effects-of-a-genome-wide-supported-variant-in-the-cacna1c-gene-on-cortical-morphology-in-schizophrenia-patients-and-healthy-subjects
#13
Fanfan Zheng, Yue Cui, Hao Yan, Bing Liu, Tianzi Jiang
Schizophrenia is a highly heritable disorder with multiple susceptibility genes. Previously, we identified CACNA1C rs2007044 as a new risk locus for schizophrenia, with the minor allele G as risk allele. This association was recently validated by a powerful genome-wide association study. However, the underlying neural mechanisms remain unclear. Therefore, we tested whether the risk allele has an influence on cortical surface area and thickness in a sample of schizophrenia patients and healthy controls. We found significant genotype by diagnosis interactions on cortical surface area, but not thickness, in the right dorsolateral prefrontal cortex and the left superior parietal cortex, both of which are key components of the central executive network...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27670918/control-of-cortex-development-by-ulk4-a-rare-risk-gene-for-mental-disorders-including-schizophrenia
#14
Bing Lang, Lei Zhang, Guanyu Jiang, Ling Hu, Wei Lan, Lei Zhao, Irene Hunter, Michal Pruski, Ning-Ning Song, Ying Huang, Ling Zhang, David St Clair, Colin D McCaig, Yu-Qiang Ding
Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for, and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia...
September 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27637363/independent-component-analysis-of-snps-reflects-polygenic-risk-scores-for-schizophrenia
#15
Jiayu Chen, Vince D Calhoun, Godfrey D Pearlson, Nora I Perrone-Bizzozero, Jessica A Turner, Stefan Ehrlich, Beng-Choon Ho, Jingyu Liu
Schizophrenia is a psychiatric disorder with high heritability. Recent genome-wide association studies have provided a list of risk loci reliably derived from unprecedentedly large samples. However, further delineation of the diagnosis-associated susceptibility variants is needed to better characterize the genetic architecture given the disease's complex nature. In this sense, a data-driven approach might hold promise for identifying functionally related clusters of genetic variants that might not be captured by hypothesis-based models...
September 13, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27629369/genome-wide-association-study-of-loneliness-demonstrates-a-role-for-common-variation
#16
Jianjun Gao, Lea K Davis, Amy B Hart, Sandra Sanchez-Roige, Lide Han, John T Cacioppo, Abraham A Palmer
Loneliness is a complex biological trait that has been associated with numerous negative health outcomes. The measurement and environmental determinants of loneliness are well understood, but its genetic basis is not. Previous studies have estimated the heritability of loneliness between 37 and 55% using twins and family-based approaches, and have explored the role of specific candidate genes. We used genotypic and phenotypic data from 10 760 individuals aged ⩾50 years that were collected by the Health and Retirement Study (HRS) to perform the first genome-wide association study of loneliness...
October 12, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27620326/association-of-cacna1c-and-syne1-in-offspring-of-patients-with-psychiatric-disorders
#17
Patricia Gassó, Vanessa Sánchez-Gistau, Sergi Mas, Gisela Sugranyes, Natalia Rodríguez, Daniel Boloc, Elena de la Serna, Soledad Romero, Dolores Moreno, Carmen Moreno, Covadonga M Díaz-Caneja, Amalia Lafuente, Josefina Castro-Fornieles
Schizophrenia (SZ) and bipolar disorder (BD) are severe mental diseases associated with cognitive impairment, mood disturbance, and psychosis. Both disorders are highly heritable and share a common genetic background. The present study assesses, for the first time, differences in genotype frequencies of polymorphisms located in genes involved in neurodevelopment and synaptic plasticity between genetic high-risk individuals (offspring of patients with SZ or BD; N=100: 31 and 69, respectively) and control subjects (offspring of community controls; N=96)...
November 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27606317/a-case-for-returning-to-multiplex-families-for-further-understanding-the-heritability-of-schizophrenia-a-psychiatrist-s-perspective
#18
Lynn E DeLisi
The genetic mechanism for schizophrenia still remains unknown despite decades of research. A tremendous amount of investigator time and effort has gone into ascertainment of clinical samples for genetic studies over the years. Most recently, a large international effort of unprecedented collaboration has occurred to combine data worldwide in pursuit of uncovering the relevant genetic risk factors. However, in the process, the use of multiplex families to understand the genetics has waned, and it has been presumed that large resources of unrelated patients and controls are more efficient to find risk alleles than families...
May 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27591410/association-study-of-dopamine-receptor-genes-polymorphisms-with-the-risk-of-schizophrenia-in-the-han-chinese-population
#19
Beimeng Yang, Weibo Niu, Shiqing Chen, Fei Xu, Xingwang Li, Xi Wu, Yanfei Cao, Rui Zhang, Fengping Yang, Lu Wang, Weidong Li, Yifeng Xu, Lin He, Guang He
Schizophrenia is a highly heritable psychiatric disorder often associated with dopamine-related genetic variations. Thus, we performed a case-control study in 1504 Han Chinese population to evaluate the association of DRD1, DRD2 and DRD3 polymorphisms with schizophrenia. No statistically significant difference in allelic or genotypic frequency was found between schizophrenia and control subjects. Strong positive linkage disequilibrium was detected among the SNPs within DRD1 and DRD2. However, no positive haplotype distribution was found to be associated with schizophrenia...
November 30, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27585752/a-cis-eqtl-in-ahi1-confers-risk-to-schizophrenia-in-european-populations
#20
Zhimin Ren, Anli Qiu, Aiqi Zhang, Lijun Huang, Shuquan Rao
Schizophrenia is a devastating mental disorder, with heritability as high as 80%. Although genome-wide association studies have identified multiple promising risk variants of schizophrenia, they could only explain a small portion of the disease heritability, and other variants with low to moderate effect remain to be identified. Abelson helper integration site 1 (AHI1) is highly expressed in mammals throughout the developing brain, with lower expression continuing into adulthood. Besides, previous evidence suggested that AHI1 expression was changed in schizophrenia patients...
October 6, 2016: Neuroscience Letters
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