scholarly journals Exome sequencing in bipolar disorder reveals shared risk gene AKAP11 with schizophrenia

2021 ◽  
Author(s):  
Duncan S Palmer ◽  
Daniel P Howrigan ◽  
Sinéad B Chapman ◽  
Rolf Adolfsson ◽  
Nick Bass ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Exome Sequencing ◽  
Meta Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Evolutionary Constraint ◽  
Risk Gene ◽  
Whole Exome ◽  
Gene Level ◽  
Shared Risk

AbstractHere we report results from the Bipolar Exome (BipEx) collaboration analysis of whole exome sequencing of 13,933 individuals diagnosed with bipolar disorder (BD), matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1 disorder (BD1) and bipolar 2 disorder (BD2). We also find an excess of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 SCZ cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from GWAS of BD, however, are not significantly enriched for ultra-rare PTVs. Combining BD gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (ultra-rare PTVs seen in 33 cases and 13 controls, OR = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 is known to interact with GSK3B, the hypothesized mechanism of action for lithium, one of the few treatments for BD. Overall, our results lend further support to the polygenic basis of BD and demonstrate a role for rare coding variation as a significant risk factor in BD onset.

scholarly journals EXOME SEQUENCING IN BIPOLAR DISORDER REVEALS SHARED RISK GENE AKAP11 WITH SCHIZOPHRENIA

2021 ◽  
Vol 51 ◽  
pp. e24
Author(s):  
Duncan Palmer ◽  
Daniel Howrigan ◽  
Rolf Adolfsson ◽  
Douglas Blackwood ◽  
Aiden Corvin ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Exome Sequencing ◽  
Risk Gene ◽  
Shared Risk

scholarly journals Sequential filtering for clinically relevant variants as a method for clinical interpretation of whole exome sequencing findings in glioma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ege Ülgen ◽  
Özge Can ◽  
Kaya Bilguvar ◽  
Cemaliye Akyerli Boylu ◽  
Şirin Kılıçturgay Yüksel ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Analysis ◽  
Clinical Interpretation ◽  
Germline Variants ◽  
Whole Exome ◽  
Gene Level ◽  
Analysis Workflow ◽  
Tumor Mutational Burden ◽  
Diffuse Gliomas

Abstract Background In the clinical setting, workflows for analyzing individual genomics data should be both comprehensive and convenient for clinical interpretation. In an effort for comprehensiveness and practicality, we attempted to create a clinical individual whole exome sequencing (WES) analysis workflow, allowing identification of genomic alterations and presentation of neurooncologically-relevant findings. Methods The analysis workflow detects germline and somatic variants and presents: (1) germline variants, (2) somatic short variants, (3) tumor mutational burden (TMB), (4) microsatellite instability (MSI), (5) somatic copy number alterations (SCNA), (6) SCNA burden, (7) loss of heterozygosity, (8) genes with double-hit, (9) mutational signatures, and (10) pathway enrichment analyses. Using the workflow, 58 WES analyses from matched blood and tumor samples of 52 patients were analyzed: 47 primary and 11 recurrent diffuse gliomas. Results The median mean read depths were 199.88 for tumor and 110.955 for normal samples. For germline variants, a median of 22 (14–33) variants per patient was reported. There was a median of 6 (0–590) reported somatic short variants per tumor. A median of 19 (0–94) broad SCNAs and a median of 6 (0–12) gene-level SCNAs were reported per tumor. The gene with the most frequent somatic short variants was TP53 (41.38%). The most frequent chromosome-/arm-level SCNA events were chr7 amplification, chr22q loss, and chr10 loss. TMB in primary gliomas were significantly lower than in recurrent tumors (p = 0.002). MSI incidence was low (6.9%). Conclusions We demonstrate that WES can be practically and efficiently utilized for clinical analysis of individual brain tumors. The results display that NOTATES produces clinically relevant results in a concise but exhaustive manner.

scholarly journals Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paddy Ssentongo ◽  
Emily S. Heilbrunn ◽  
Anna E. Ssentongo ◽  
Shailesh Advani ◽  
Vernon M. Chinchilli ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Beneficial Effects ◽  
Risk Of Mortality ◽  
Immunodeficiency Syndrome ◽  
Hiv Negative

AbstractSusceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05–1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21–2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.

scholarly journals Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yoshiro Morimoto ◽  
Mihoko Shimada-Sugimoto ◽  
Takeshi Otowa ◽  
Shintaro Yoshida ◽  
Akira Kinoshita ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variant ◽  
Rare Variant Association ◽  
Association Tests ◽  
Risk Gene ◽  
Whole Exome

scholarly journals Prevalence and Determinants of Low Birth Weight in Ethiopia: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Nuradin Abusha Katiso ◽  
Getachew Mullu Kassa ◽  
Gedefaw Abeje Fekadu ◽  
Abadi Kidanemariam Berhe ◽  
Achenef Asmamaw Muche
Keyword(s):  
Birth Weight ◽  
Prenatal Care ◽  
Low Birth Weight ◽  
Rural Areas ◽  
Meta Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Pooled Prevalence ◽  
Unpublished Studies ◽  
Meta Analyses

Introduction. Low birth weight (LBW) is the most significant risk factor for neonatal and infant mortality. It is one of the major public health problems in developing countries. Although there are various studies on low birth weight, findings were inconsistent and inconclusive. Therefore, this study was conducted to estimate the national-pooled prevalence of low birth weight and its associated factors in Ethiopia. Method. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. This meta-analysis employed a review of both published and unpublished studies conducted in Ethiopia. The databases used were PubMed, Google Scholar, CINAHL, and African Journals Online. Relevant search terms for prevalence and determinants of LBW were used to retrieve articles. The meta-analysis was conducted using STATA 14 software. Forest plots were used to present the findings. The Cochran Q test and I2 test statistics were used to test heterogeneity across studies. Egger’s test was used to assess the publication bias of included studies. The pooled prevalence and the odds ratios (OR) with 95% confidence intervals (CI) were computed and were presented using forest plots. Results. A total of 28 studies, 50,110 newborn babies, were included in this meta-analysis. The pooled prevalence of LBW in Ethiopia was 14.1% (95% CI = 11.2, 17.1). Higher variation in the prevalence of LBW in different regions across the country was observed. Significant association of LBW with sex of the newborn baby, higher odds among female babies (OR = 1.5 (95% CI = 1.2, 1.7)), prematurity (OR = 4.7 (95% CI = 1.5, 14.5)), not attending prenatal care (OR = 1.7 (95% CI = 1.4, 2.2)), pregnancy-induced hypertension (OR = 6.7 (95% CI = 3.5, 12.9)), and newborn babies whose mothers were from rural areas (OR = 1.8 (95% CI = 1.2, 2.6) were the factors associated with low birth weight. Conclusions. The prevalence of LBW in Ethiopia was high. LBW was associated with several maternal and newborn characteristics. The large disparity of LBW among the different regions in the country needs targeted intervention in areas with higher prevalence. Particular emphasis should be given to mothers residing in rural areas. Community-based programs are important to increase the use of prenatal care.

scholarly journals Smoking and Incidence of Insomnia: a systematic review and meta-analysis of cohort studies

2020 ◽  
Author(s):  
Nan Hu ◽  
Chunyi Wang ◽  
Yan Liao ◽  
Qichen Dai ◽  
Shiyi Cao
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Pooled Analysis ◽  
Study Characteristics ◽  
Meta Analyses ◽  
The Impact

Abstract Background: Both smoking and insomnia are worldwide problems and this study aims to investigate the impact of smoking on the incidence of insomnia. Methods: PubMed, EMBASE and OVID were searched through March, 2020. Cohort studies reporting the effect of smoking on the incidence of insomnia were included. We quantitatively analyzed the basic framework and study characteristics, and then pooled estimate effects with 95% confidence intervals (CIs) of outcomes of each included studies using fixed-effects meta-analyses. Results: This systematic review included six cohort studies involving 12445 participants. Quantitatively summarized results suggested smoking could significantly increase the incidence of insomnia (OR: 1.07, 95%CI: 1.02,1.13). Regular smoking was significantly associated with incidence of insomnia (OR=1.07, 95% CI:1.01,1.13). As for occasional smokers and ex-smokers, the pooled analysis didn’t indicate a significant association (occasional smoker: OR=2.09, 95% CI:0.44,9.95; ex-smoker; OR=1.02, 95% CI:0.67,1.54). Subgroup analysis by age, gender ratio and region showed statistically significant relationship between smoking and incidence of insomnia in specific groups. Conclusions: Integrated longitudinal observational evidence identified smoking as a significant risk factor of insomnia. Considering the limited amount of available studies, more high-quality and prospective cohort studies of large sample sizes are needed to explore details of this association.

scholarly journals Serological markers and risk factors for hepatitis B and C viruses in patients infected with human immunodeficiency virus

2006 ◽  
Vol 48 (6) ◽  
pp. 321-326 ◽  
Author(s):  
Alvaro Hoyos-Orrego ◽  
Mónica Massaro-Ceballos ◽  
Marta Ospina-Ospina ◽  
Carolina Gómez-Builes ◽  
Nora Vanegas-Arroyave ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis B ◽  
Significant Risk ◽  
Low Frequency ◽  
Significant Risk Factor ◽  
Hbv Infection ◽  
Serological Markers ◽  
Rt Pcr ◽  
Molecular Approaches ◽  
Shared Risk

Both hepatitis B and hepatitis C viruses (HBV and HCV) infection are common in HIV-infected individuals as a result of shared risk factors for acquisition. A serological study for HBV and HCV was performed in 251 HIV-positive individuals from Medellín, Colombia. A qualitative RT-PCR for HCV was done in 90 patients with CD4+ T-cell count < 150 per mm³. Serological markers for HBV infection were present in 97 (38.6%) patients. Thirty six of them (37.1%) had isolated anti-HBc. A multivariate analysis indicated that the following risk factors were significantly associated with the presence of these markers: age (OR = 1.05, 95% CI: 1.01-1.08), pediculosis pubis (OR = 1.83, 95% CI: 1.01-3.33), men who have sex with men and women (OR = 3.23, 95% CI: 1.46-7.13) and men who have sex only with men (OR = 3.73, 95% CI: 1.58-8.78). The same analysis restricted to women showed syphilis as the only significant risk factor. Thus, HBV infection was considerably associated with high risk sexual behavior. HCV was present in only two (0.8%) of HIV patients. Both of them were positive by RT-PCR and anti-HCV. This low frequency of HIV/HCV coinfection was probably due to the uncommon intravenous drug abuse in this population. The frequent finding of isolated anti-HBc warrants molecular approaches to rule out the presence of cryptic HBV infection.

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