collection
https://read.qxmd.com/read/27167565/genome-wide-association-studies-of-posttraumatic-stress-disorder-in-2-cohorts-of-us-army-soldiers
#1
JOURNAL ARTICLE
Murray B Stein, Chia-Yen Chen, Robert J Ursano, Tianxi Cai, Joel Gelernter, Steven G Heeringa, Sonia Jain, Kevin P Jensen, Adam X Maihofer, Colter Mitchell, Caroline M Nievergelt, Matthew K Nock, Benjamin M Neale, Renato Polimanti, Stephan Ripke, Xiaoying Sun, Michael L Thomas, Qian Wang, Erin B Ware, Susan Borja, Ronald C Kessler, Jordan W Smoller
IMPORTANCE: Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity. OBJECTIVE: To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). DESIGN, SETTING, AND PARTICIPANTS: Two coordinated genome-wide association studies of mental health in the US military contributed participants...
July 1, 2016: JAMA Psychiatry
https://read.qxmd.com/read/26404826/genetics-and-genomics-of-psychiatric-disease
#2
REVIEW
Daniel H Geschwind, Jonathan Flint
Large-scale genomic investigations have just begun to illuminate the molecular genetic contributions to major psychiatric illnesses, ranging from small-effect-size common variants to larger-effect-size rare mutations. The findings provide causal anchors from which to understand their neurobiological basis. Although these studies represent enormous success, they highlight major challenges reflected in the heterogeneity and polygenicity of all of these conditions and the difficulty of connecting multiple levels of molecular, cellular, and circuit functions to complex human behavior...
September 25, 2015: Science
https://read.qxmd.com/read/26176920/sparse-whole-genome-sequencing-identifies-two-loci-for-major-depressive-disorder
#3
JOURNAL ARTICLE
(no author information available yet)
Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2...
July 30, 2015: Nature
https://read.qxmd.com/read/25980509/pharmacogenetics-of-major-depressive-disorder-top-genes-and-pathways-toward-clinical-applications
#4
REVIEW
Chiara Fabbri, Alessandro Serretti
The pharmacogenetics of antidepressants has been not only a challenging but also frustrating research field since its birth in the 1990s. Indeed, great expectations followed the first evidence of familiar aggregation of antidepressant response. Despite the progress from candidate gene studies to genome-wide association studies (GWAS), results fell out the expectations and they were often inconsistent. Anyway, the cumulative evidence supports the involvement of some genes and molecular pathways in antidepressant efficacy...
July 2015: Current Psychiatry Reports
https://read.qxmd.com/read/23020879/genetic-basis-of-intellectual-disability
#5
REVIEW
Jay W Ellison, Jill A Rosenfeld, Lisa G Shaffer
In the past decade, we have witnessed a flood of reports about mutations that cause or contribute to intellectual disability (ID). This rapid progress has been driven in large part by the implementation of chromosomal microarray analysis and next-generation sequencing methods. The findings have revealed extensive genetic heterogeneity for ID, as well as examples of a common genetic etiology for ID and other neurobehavioral/psychiatric phenotypes. Clinical diagnostic application of these new findings is already well under way, despite incomplete understanding of non-Mendelian transmission patterns that are sometimes observed...
2013: Annual Review of Medicine
https://read.qxmd.com/read/25979620/epigenetics-of-posttraumatic-stress-disorder-current-evidence-challenges-and-future-directions
#6
REVIEW
Anthony S Zannas, Nadine Provençal, Elisabeth B Binder
Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation. An increasing body of evidence in human subjects with PTSD supports a role for epigenetic regulation of distinct genes and pathways in the pathogenesis of PTSD. The role of epigenetic regulation is further supported by studies examining fear conditioning in rodent models...
September 1, 2015: Biological Psychiatry
https://read.qxmd.com/read/25738232/heritability-of-autism-spectrum-disorder-in-a-uk-population-based-twin-sample
#7
JOURNAL ARTICLE
Emma Colvert, Beata Tick, Fiona McEwen, Catherine Stewart, Sarah R Curran, Emma Woodhouse, Nicola Gillan, Victoria Hallett, Stephanie Lietz, Tracy Garnett, Angelica Ronald, Robert Plomin, Frühling Rijsdijk, Francesca Happé, Patrick Bolton
IMPORTANCE: Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population. OBJECTIVES: To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD...
May 2015: JAMA Psychiatry
https://read.qxmd.com/read/25765319/epigenetic-mechanisms-of-chronic-pain
#8
REVIEW
Giannina Descalzi, Daigo Ikegami, Toshikazu Ushijima, Eric J Nestler, Venetia Zachariou, Minoru Narita
Neuropathic and inflammatory pain promote a large number of persisting adaptations at the cellular and molecular level, allowing even transient tissue or nerve damage to elicit changes in cells that contribute to the development of chronic pain and associated symptoms. There is evidence that injury-induced changes in chromatin structure drive stable changes in gene expression and neural function, which may cause several symptoms, including allodynia, hyperalgesia, anxiety, and depression. Recent findings on epigenetic changes in the spinal cord and brain during chronic pain may guide fundamental advances in new treatments...
April 2015: Trends in Neurosciences
https://read.qxmd.com/read/25152434/genetic-risk-for-schizophrenia-convergence-on-synaptic-pathways-involved-in-plasticity
#9
REVIEW
Jeremy Hall, Simon Trent, Kerrie L Thomas, Michael C O'Donovan, Michael J Owen
Recent large-scale genomic studies have revealed two broad classes of risk alleles for schizophrenia: a polygenic component of risk mediated through multiple common risk variants and rarer more highly penetrant submicroscopic chromosomal deletions and duplications, known as copy number variants. The focus of this review is on the emerging findings from the latter and subsequent exome sequencing data of smaller, deleterious single nucleotide variants and indels. In these studies, schizophrenia patients were found to have enriched de novo mutations in genes belonging to the postsynaptic density at glutamatergic synapses, particularly components of the N-methyl-D-aspartate receptor signaling complex, including the PSD-95 complex, activity-regulated cytoskeleton-associated protein interactors, the fragile X mental retardation protein complex, voltage-gated calcium channels, and genes implicated in actin cytoskeletal dynamics...
January 1, 2015: Biological Psychiatry
https://read.qxmd.com/read/25005482/mobile-dna-elements-in-the-generation-of-diversity-and-complexity-in-the-brain
#10
REVIEW
Jennifer A Erwin, Maria C Marchetto, Fred H Gage
Mobile elements are DNA sequences that can change their position (retrotranspose) within the genome. Although its biological function is largely unappreciated, DNA derived from mobile elements comprises nearly half of the human genome. It has long been thought that neuronal genomes are invariable; however, recent studies have demonstrated that mobile elements actively retrotranspose during neurogenesis, thereby creating genomic diversity between neurons. In addition, mounting data demonstrate that mobile elements are misregulated in certain neurological disorders, including Rett syndrome and schizophrenia...
August 2014: Nature Reviews. Neuroscience
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