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Schizophrenia Bulletin Jul 2017Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with... (Meta-Analysis)
Meta-Analysis Review
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. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population.
Topics: Aptitude; Cognition; Cognitive Dysfunction; Endophenotypes; Executive Function; Humans; Intelligence; Schizophrenia
PubMed: 27872257
DOI: 10.1093/schbul/sbw146 -
Science Progress 2023The purpose of this meta-analysis was to strengthen the credibility of primary research results by combining open-source scientific material, namely a comparison of... (Meta-Analysis)
Meta-Analysis Review
The purpose of this meta-analysis was to strengthen the credibility of primary research results by combining open-source scientific material, namely a comparison of craniofacial features (Cfc) between Crouzon's syndrome (CS) patients and non-CS populations. All articles published up to October 7, 2021, were included in the search of PubMed, Google Scholar, Scopus, Medline, and Web of Science. The PRISMA guidelines were followed to conduct this study. PECO framework was applied in the following ways: Those who have CS are denoted by the letter P, those who have been diagnosed with CS via clinical or genetic means by the letter E, those who do not have CS by the letter C, and those who have a Cfc of CS by the letter O. Independent reviewers collected the data and ranked the publications based on their adherence to the Newcastle-Ottawa Quality Assessment Scale. A total of six case-control studies were reviewed for this meta-analysis. Due to the large variation in cephalometric measures, only those published in at least two previous studies were included. This analysis found that CS patients had a smaller skull and mandible volumes than those without CS.in terms of SNA° (MD = -2.33, = <0.001, = 83.6%) and ANB°(MD = -1.89, = <0.005, = 93.1%)), as well as ANS (MD = -1.87, = 0.001, = 96.5%)) and SN/PP (MD = -1.99, = 0.036, = 77.3%)). In comparison to the general population, people with CS tend to have shorter and flatter cranial bases, smaller orbital volumes, and cleft palates. They differ from the general population in having a shorter skull base and more V-shaped maxillary arches.
Topics: Humans; Craniofacial Dysostosis; Case-Control Studies
PubMed: 36803068
DOI: 10.1177/00368504231156297 -
Environmental Health and Preventive... Nov 2017The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The p.R4810K and other rare variants of ring finger protein 213 gene (RNF213) were illustrated as susceptibility variants for moyamoya (MMD) and non-moyamoya intracranial artery stenosis/occlusion disease (ICASO) recently. However, the effect sizes of p.R4810K were in great discrepancy even in studies of the same ethnic population and firm conclusions of other rare variants have been elusive given the small sample sizes and lack of replication. Thus, we performed this study to quantitatively evaluate whether or to what extent the rare variants of RNF213 contribute to MMD and ICASO in different populations.
METHODS
A systematic search of PubMed, EMBASE, ISI web of science, CNKI, and WANFANG DATA was conducted up to 5 September 2017. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effect models based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity and family history. Sensitivity and publication bias analysis were performed to test the robustness of associations. All the statistical analyses were conduct using STATA 12.0.
RESULTS
Twenty studies including 2353 MMD cases and 5488 controls and 11 studies including 1778 ICASO cases and 3140 controls were included in this study. Pooled ORs indicated that RNF213 p.R4810K significantly increased MMD and ICASO risk in East Asians with great effect sizes of discrepancy (dominant model: odds ratios 184.04, 109.77, and 31.53 and 10.07, 28.52, and 5.59 for MMD and ICASO, respectively, in Japan, Korea, and China). It significantly increased familial MMD risk in Japan, Korea, and China with 5 ~ 36 times larger effect sizes than that for sporadic ones in each country (dominant model ORs 1802.44, 512.42, 1109.02 and 134.35, 99.82, and 30.52, respectively, for familial and sporadic cases). The effect sizes of RNF213 p.R4810K to sporadic MMD were 3 ~ 4 times larger in Japan and Korea than those in China. RNF213 p.R4810K also increased the ICASO risk in Japan and Korea with 2 ~ 4 times larger effect sizes than that in China (dominant model ORs 10.71, 28.52, and 5.59, respectively). Another two rare variants- p.E4950D and p.A5021V significantly increased MMD risk in Chinese population (dominant model ORs 9.06 and 5.01, respectively). Various other rare variants in RNF213 were identified in Japanese, Chinese, European, and Hispanic American populations without association evidence available yet.
CONCLUSIONS
This meta-analysis shows the critical roles of RNF213 p.R4810K in MMD especially familial MMD and ICASO in Japan, Korea, and China. Except for RNF213 p.R4810K, MMD seems to have more complex determiners in China. Distinct genetic background exists and other environmental or genetic factor(s) may contribute to MMD. Studies focused on delineating the ethnicity-specific factors and pathological role of RNF213 variants in MMD and ICASO are needed.
Topics: Adenosine Triphosphatases; Arterial Occlusive Diseases; Carotid Artery Diseases; Constriction, Pathologic; Genetic Predisposition to Disease; Genetic Variation; Humans; Moyamoya Disease; Ubiquitin-Protein Ligases
PubMed: 29165161
DOI: 10.1186/s12199-017-0680-1 -
American Journal of Alzheimer's Disease... Sep 2015Large-scale genome-wide association studies have identified TREM2 variants to be significantly associated with Alzheimer's disease (AD) in caucasian population. The goal... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Large-scale genome-wide association studies have identified TREM2 variants to be significantly associated with Alzheimer's disease (AD) in caucasian population. The goal of this systematic study and meta-analysis was to assess the association between Triggering receptor expressed on myeloid cells 2 (TREM2) variants and AD in East Asian population.
METHODS
In this study, literatures were searched in PubMed, MEDLINE, EMBASE, and the Cochrane library to screen citations from January 1990 to June 2014. Data analysis was done by using the Stata 12 software.
RESULTS
Twelve studies were considered for analysis. A total of 13 535 patients with AD and 22 976 healthy controls were studied. The results showed that rs75932628 variant was significantly associated with AD in caucasian population (P < .001, odds ratio ¼ 3.17, 95% confidence interval 2.45-4.09). However, the association was not found in East Asian population.
CONCLUSION
In our study, we found that TREM2 variant is likely not associated with AD in East Asian population.
Topics: Alzheimer Disease; Asian People; Asia, Eastern; Humans; Membrane Glycoproteins; Receptors, Immunologic; White People
PubMed: 25852195
DOI: 10.1177/1533317515577128 -
The Journal of International Medical... Dec 2013A substantial percentage (8%) of all newly diagnosed cancer cases are in patients with previous tumours, with a similar trend in lung cancer. Cases of multiple primary... (Review)
Review
A substantial percentage (8%) of all newly diagnosed cancer cases are in patients with previous tumours, with a similar trend in lung cancer. Cases of multiple primary lung cancer (MPLC) are increasing worldwide, due to improved diagnostic and surveillance mechanisms and the ageing population. Diagnosis of MPLC is complicated by difficulties in distinguishing it from lung cancer metastasis. Clinicopathological assessment, diagnosis and management have evolved, but remain severely limited by the lack of robust and dependable molecular markers for the differential diagnosis of metastasis and MPLC. This systematic review evaluates diagnostic criteria for MPLC, and the subsequent management and success rates. The incorporation of molecular biology techniques into the diagnostic process for MPLC is also discussed.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Neoplasms, Multiple Primary; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins
PubMed: 24265329
DOI: 10.1177/0300060513504707 -
Journal of Vector Borne Diseases 2022Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming... (Review)
Review
BACKGROUND & OBJECTIVES
Dengue virus (DENV) is an RNA virus that infects approximately 2.5 billion people around the world. The incidence of dengue fever has rapidly increased at an alarming rate in the last few years and has affected thousands of people in Pakistan. This review explores the prevalence, serotypes and pathogenesis of dengue virus circulating in Pakistan.
METHODS
A systematic review of observational studies published between 1994 and December 2019 was performed. All records of the confirmed outbreak of dengue fever in Pakistan were reviewed and articles containing no primary data were excluded.
RESULTS
Four identified serotypes of dengue virus (DENV 1-4) circulate in different regions of the world causing epidemics. The most prevalent serotype, which is still epidemic and dominant in Pakistan, is DENV-2. Many factors like over-population, rapid urbanization, travelling, lack of vector control in dengue endemic areas and inadequate health-care are responsible of dynamic and huge raise of dengue in Pakistan.
INTERPRETATION & CONCLUSION
Currently there is no specific treatment for prevention of dengue virus. Recently some antiviral compounds were being tested to eradicate this disease. There is a need to develop an efficient and safe vaccine for all four serotypes to combat dengue viral infection globally and particularly in Pakistan.
Topics: Antiviral Agents; Dengue; Dengue Virus; Humans; Pakistan; Serogroup
PubMed: 36124476
DOI: 10.4103/0972-9062.331412 -
The Oncologist Apr 2017The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of... (Review)
Review
OBJECTIVE
The objective of this study was to review the role of bilateral salpingo-oophorectomy in mutation (m) carriers and alternative interventions in risk reduction of ovarian cancer (OC).
MATERIALS AND METHODS
A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in m carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention.
RESULTS
Risk-reducing bilateral salpingo-oophorectomy is an effective intervention, but its associated morbidity is substantial and seems to curtail uptake rates among the target population. Although there is much interest and a strong theoretical basis for salpingectomy with delayed oophorectomy, data on its clinical application are scarce with regard to screening, the use of an algorithmic protocol has recently shown favorable albeit indefinite results in average-risk postmenopausal women. Its incorporation into studies focused on high-risk women might help solidify a future role for screening as a bridge to surgery. The use of oral contraceptives for chemoprevention is well supported by epidemiologic studies. However, there is a lack of evidence for advocating any of the other agents proposed for this purpose, including nonsteroidal anti-inflammatory drugs, vitamin D, and retinoids.
CONCLUSION
Further studies are needed before salpingectomy with delayed oophorectomy or intensive surveillance can be offered as acceptable, less morbid alternatives to upfront oophorectomy for m carriers. 2017;22:450-459 IMPLICATIONS FOR PRACTICE: Risk-reducing bilateral salpingo-oophorectomy is currently the most effective method for reducing the risk of ovarian cancer in mutation (m) carriers. Unfortunately, it is associated with significant short- and long-term morbidity, stemming from reduced circulating estrogen. In recent years, much research has been devoted to evaluating less morbid alternatives, especially multimodal cancer screening and prophylactic salpingectomy with delayed oophorectomy. This review describes the present state of the art, with the aim of informing the counseling provided to m carriers on this complicated issue and encouraging additional research to facilitate the incorporation of such alternatives into routine practice.
Topics: BRCA1 Protein; BRCA2 Protein; Female; Heterozygote; Humans; Mutation; Ovarian Neoplasms; Risk Factors; Salpingo-oophorectomy
PubMed: 28314837
DOI: 10.1634/theoncologist.2016-0444 -
PloS One 2017The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients.
METHODS
The PubMed, Cochrane Library, Medline, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant studies. The RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random-effects models were applied depending on the presence of heterogeneity. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations between EpCAM and gastric cancer. For the significant heterogeneity studies, sensitivity analyses were applied based on the population to test the robustness of the pooled results and identify possible sources of heterogeneity.
RESULTS
A total of 11 studies including 1960 GC patients met our inclusion criteria. The results of the meta-analyses revealed that there were significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95% CI: 2.13~4.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI: 29.21~220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.23~6.27, P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95% CI:0.29~0.99, P = 0.05). No significant associations were identified between EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.66~1.19, P = 0.43), age (OR = 1.13, 95% CI: 0.58~2.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.79~6.45, P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.20~22.69, P = 0.52), TNM stage (OR = 5.14, 95% CI: 0.77~34.37, P = 0.09), Lauren type (OR = 1.18, 95% CI: 0.08~16.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24). However, due to significant heterogeneity in tumor stage, lymph node metastasis, TNM stage, differentiation and Lauren type, these results should be taken carefully.
CONCLUSIONS
The meta-analysis demonstrated that the expression of EpCAM in the gastric cancer group was greater than that in the control group. Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode metastasis and worse prognosis in gastric cancer. Due to significant heterogeneity, the sensitivity analysis suggests that population factor may be an important source of heterogeneity, and these results should be treated with caution. EpCAM may be useful as a novel prognostic factor, and large-scale and well-designed studies are needed to validate our results in the future.
Topics: Biomarkers, Tumor; Epithelial Cell Adhesion Molecule; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Prognosis; Stomach; Stomach Neoplasms; Up-Regulation
PubMed: 28403178
DOI: 10.1371/journal.pone.0175357 -
Respiratory Research Feb 2019Asthma is a common complex chronic, inflammatory polygenic disease with heterogeneous manifestations, affecting individuals of all age groups and posing an immense... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asthma is a common complex chronic, inflammatory polygenic disease with heterogeneous manifestations, affecting individuals of all age groups and posing an immense burden on healthcare resources. A number of studies have identified the association between a disintegrin and metalloprotease 33 (ADAM33) polymorphisms and asthma risk, however, the results still remain inconclusive. The objective of the present study was to identify the effect of ADAM33 variants in asthma susceptibility.
METHODS
Eligible case-control studies published between January 2000 and June 2018 was searched and retrieved from online electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the effect.
RESULTS
A total of 63 case-control studies were finally screened out, including 13,280 asthma patients and 13,340 controls. Eleven SNPs of ADAM33 gene were identified. Our results detected a significant association between ADAM33 T2, Q1, F + 1 and AA genotype of T + 1 polymorphisms and asthma risk in total population. Subgroup analysis by ethnicities showed that the alleles and genotypes of T2, Q1 and F + 1 polymorphisms were associated with asthma susceptibility among Asian populations, while V4 polymorphism was associated with asthma among Caucasian populations. Subgroup analysis by ages showed that T2, F + 1 and ST + 4 polymorphisms were associated with childhood asthma, while Q1 and V4 polymorphisms were associated with asthma risk in adults. Subgroup analysis by asthma severity showed that only the G allele of ADAM33 T1 polymorphism was associated with the severity of asthma when compared with the controls. In addition, T2, Q1 and F + 1 polymorphisms of ADAM33 were significantly associated with increased the asthma risk in Chinese asthma patients.
CONCLUSIONS
Our results found that T2, Q1 and F + 1 polymorphisms of ADAM33 gene might contribute to asthma risk. Future well-designed case-control studies with large population and more ethnicities are still needed to estimate the association.
Topics: ADAM Proteins; Asthma; Case-Control Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 30791911
DOI: 10.1186/s12931-019-1006-1 -
International Journal of Molecular... Oct 2022Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to... (Review)
Review
Research in traumatic brain injury (TBI) is an urgent priority, as there are currently no TBI biomarkers to assess the severity of injury, to predict outcomes, and to monitor recovery. Small non-coding RNAs (sncRNAs) including microRNAs can be measured in saliva following TBI and have been investigated as potential diagnostic markers. The aim of this systematic review was to investigate the diagnostic or prognostic ability of microRNAs extracted from saliva in human subjects. PubMed, Embase, Scopus, PsycINFO and Web of Science were searched for studies that examined the association of saliva microRNAs in TBI. Original studies of any design involving diagnostic capacity of salivary microRNAs for TBI were selected for data extraction. Nine studies met inclusion criteria, with a heterogeneous population involving athletes and hospital patients, children and adults. The studies identified a total of 188 differentially expressed microRNAs, with 30 detected in multiple studies. MicroRNAs in multiple studies involved expression change bidirectionality. The study design and methods involved significant heterogeneity that precluded meta-analysis. Early data indicates salivary microRNAs may assist with TBI diagnosis. Further research with consistent methods and larger patient populations is required to evaluate the diagnostic and prognostic potential of saliva microRNAs.
Topics: Adult; Child; Humans; MicroRNAs; Brain Injuries, Traumatic; Biomarkers; Saliva
PubMed: 36361944
DOI: 10.3390/ijms232113160