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Heritability of schizophrenia

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...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
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...
October 12, 2016: JAMA Psychiatry
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
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...
October 11, 2016: Molecular Psychiatry
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
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
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
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
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
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
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
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
Xiaodi Jia, Tianxiao Zhang, Lu Li, Dongke Fu, Huali Lin, Gang Chen, Xinshe Liu, Fanglin Guan
Schizophrenia (SCZ) is a complex neuropsychiatric disorder with high heritability. Abnormal gene methylation was found to play a key role in the development of SCZ, suggesting that histone deacetylases (HDACs) may increase the expression of several key genes in the brain. However, recent studies evaluating the association between SCZ and genetic polymorphisms in histone deacetylase 3 (encoded by HDAC3) have shown conflicting results. In this study, we designed a two-stage case-control study to investigate the association of the HDAC3 with SCZ...
August 30, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Eilis Hannon, Emma Dempster, Joana Viana, Joe Burrage, Adam R Smith, Ruby Macdonald, David St Clair, Colette Mustard, Gerome Breen, Sebastian Therman, Jaakko Kaprio, Timothea Toulopoulou, Hilleke E Hulshoff Pol, Marc M Bohlken, Rene S Kahn, Igor Nenadic, Christina M Hultman, Robin M Murray, David A Collier, Nick Bass, Hugh Gurling, Andrew McQuillin, Leonard Schalkwyk, Jonathan Mill
BACKGROUND: Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved in disease pathogenesis and how their function is regulated. RESULTS: We performed a multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in a total of 1714 individuals from three independent sample cohorts...
2016: Genome Biology
Robert A Power, Katherine E Tansey, Henriette Nørmølle Buttenschøn, Sarah Cohen-Woods, Tim Bigdeli, Lynsey S Hall, Zoltán Kutalik, S Hong Lee, Stephan Ripke, Stacy Steinberg, Alexander Teumer, Alexander Viktorin, Naomi R Wray, Volker Arolt, Bernard T Baune, Dorret I Boomsma, Anders D Børglum, Enda M Byrne, Enrique Castelao, Nick Craddock, Ian W Craig, Udo Dannlowski, Ian J Deary, Franziska Degenhardt, Andreas J Forstner, Scott D Gordon, Hans J Grabe, Jakob Grove, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Lynne J Hocking, Georg Homuth, Jouke J Hottenga, Stefan Kloiber, Jesper Krogh, Mikael Landén, Maren Lang, Douglas F Levinson, Paul Lichtenstein, Susanne Lucae, Donald J MacIntyre, Pamela Madden, Patrik K E Magnusson, Nicholas G Martin, Andrew M McIntosh, Christel M Middeldorp, Yuri Milaneschi, Grant W Montgomery, Ole Mors, Bertram Müller-Myhsok, Dale R Nyholt, Hogni Oskarsson, Michael J Owen, Sandosh Padmanabhan, Brenda W J H Penninx, Michele L Pergadia, David J Porteous, James B Potash, Martin Preisig, Margarita Rivera, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Johannes H Smit, Blair H Smith, Hreinn Stefansson, Kari Stefansson, Jana Strohmaier, Patrick F Sullivan, Pippa Thomson, Thorgeir E Thorgeirsson, Sandra Van der Auwera, Myrna M Weissman, Gerome Breen, Cathryn M Lewis
BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting...
May 24, 2016: Biological Psychiatry
E M Frans, P Lichtenstein, C M Hultman, R Kuja-Halkola
BACKGROUND: Advancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages...
October 2016: Psychological Medicine
Carolyn E Cesta, Mattias Månsson, Camilla Palm, Paul Lichtenstein, Anastasia N Iliadou, Mikael Landén
Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associations. Using the Swedish national registers, we identified all women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings (n=25,921), plus matched individuals (1:10/100) from the general population and their full-siblings...
November 2016: Psychoneuroendocrinology
Zhen Li, Tingting Shen, Ran Xin, Baoyun Liang, Juan Jiang, Weijun Ling, Bo Wei, Li Su
BACKGROUND: Schizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between the NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms and SZ in a Chinese population. METHODS: This study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han)...
July 27, 2016: Acta Neuropsychiatrica
Zhenming Guo, Weibo Niu, Yan Bi, Rui Zhang, Decheng Ren, Jiaxin Hu, Xiaoye Huang, Xi Wu, Yanfei Cao, Fengping Yang, Lu Wang, Weidong Li, Xingwang Li, Yifeng Xu, Lin He, Tao Yu, Guang He
Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population...
September 6, 2016: Neuroscience Letters
Yu-Wen Liu, Nian-Sheng Tzeng, Chin-Bin Yeh, Terry B J Kuo, San-Yuan Huang, Chuan-Chia Chang, Hsin-An Chang
Reduced resting heart rate variability (HRV) has been observed in patients with schizophrenia and their relatives, suggesting genetic predispositions. However, findings have not been consistent. We assessed cardiac autonomic response to deep breathing in first-degree relatives of patients with schizophrenia (n=45; 26 female; aged 39.69±14.82 years). Data were compared to healthy controls (n=45; 26 female; aged 38.27±9.79 years) matched for age, gender, body mass index and physical activity as well as to unmedicated patients with acute schizophrenia (n=45; 25 female; aged 37...
September 30, 2016: Psychiatry Research
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