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Sökning: WFRF:(Melle I.)

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  • Marshall, Christian R., et al. (författare)
  • Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:1, s. 27-35
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.</p>
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  • Onyeka, I. N., et al. (författare)
  • Comorbidity of Physical Disorders Among Patients With Severe Mental Illness With and Without Substance Use Disorders: A Systematic Review and Meta-Analysis
  • 2019
  • Ingår i: Journal of Dual Diagnosis. - 1550-4263. ; 15:3, s. 192-206
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Physical disorders in patients with severe mental illness (SMI) are common and they tend to be underdiagnosed by clinicians, which might lead to negative treatment outcomes. The presence of substance use disorders could further aggravate the situation. There are existing systematic reviews on physical disorders among individuals with SMI in general but none of these previous reviews stratified their findings by substance use disorder status. This study aimed to synthesize the evidence on the frequency of comorbid physical disorders among patients with SMI with or without substance use disorders. Methods: We searched for studies published in English between 1988 and 2017 in MEDLINE, Embase, CINAHL, PsycINFO, Global Health, Web of Science, Scopus, WHO Global Health Library (Global Index Medicus), Google Scholar, OpenGrey, the Grey Literature Report, Cochrane Library, International Standardized Randomized Controlled Trial Number Registry, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Australian and New Zealand Clinical Trials Registry, and PROSPERO. There was no geographical restriction and the target population was adults (>= 18 years) with diagnosed SMI including schizophrenia, bipolar disorder, and other psychotic illnesses. The outcome of interest was physical disorder. Results: A total of 6,994 records were retrieved. Only 30 papers (representing 24 studies) met our inclusion criteria and 13 studies were included in the meta-analysis. The prevalence of most of the reported physical disorders was higher in SMI patients with substance use disorders than in those without substance use disorders. When ranked according to pooled prevalence level, hypertension (35.6%), tardive dyskinesia (35.4%), and hepatitis C (26.9%) were the most prevalent physical disorders among SMI patients with substance use disorders. For SMI patients without substance use disorders, hypertension (32.5%), tardive dyskinesia (25.1%), and endocrine disease (19.0%) were more common. Estimates for diabetes (7.5% vs. 7.5%) and cardiovascular diseases (11.8% vs. 11.3%) were similar across groups. Conclusions: Physical disorders among SMI patients vary by substance use disorder status. Clinicians managing SMI in patients should screen for physical disorders and substance use disorders and provide treatment or referral. Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42017072286.
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  • Ripke, Stephan, et al. (författare)
  • Biological insights from 108 schizophrenia-associated genetic loci
  • 2014
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 511:7510, s. 421-427
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.</p>
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