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Gene Dec 2023Identification of genetic risk factors for PCOS susceptibility. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Identification of genetic risk factors for PCOS susceptibility.
OBJECTIVE
To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways.
DATA SOURCES
Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2.
MAIN OUTCOMES
Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk.
RESULTS
Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795.
CONCLUSION
and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations.
Topics: Female; Humans; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Genetic Predisposition to Disease; Interleukin-6; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 37714276
DOI: 10.1016/j.gene.2023.147796 -
Genetics in Medicine : Official Journal... Jun 2023Microcosting can provide valuable economic evidence to inform the translation of genomic sequencing to clinical practice. A systematic literature review was conducted to... (Review)
Review
PURPOSE
Microcosting can provide valuable economic evidence to inform the translation of genomic sequencing to clinical practice. A systematic literature review was conducted to identify studies employing microcosting methods to estimate the cost of genomic sequencing to diagnose cancer and rare diseases.
METHODS
Four electronic databases, Medline, Embase, EconLit, and Cumulated Index to Nursing and Allied Health Literature were searched. Reference lists of identified studies were also searched. Studies were included if they had estimated the cost of genome sequencing or exome sequencing for cancer or rare disease diagnosis using microcosting methods.
RESULTS
Seven studies met the inclusion criteria. Cost estimates for genome sequencing and exome sequencing ranged between US$2094 and $9706 and US$716 and $4817 per patient, respectively. All studies disaggregated resource use and cost inputs into labor, equipment, and consumables, with consumables being the main cost component. Considerable differences in the level of detail used to report the steps and resources used in each of the sequencing steps limited study comparisons.
CONCLUSION
Defining a standard microcosting methodology is challenging because of the heterogeneous nature of genomic sequencing. Reporting of detailed and complete sequencing procedures, inclusion of sensitivity analyses and clear justifications of resource use, and measurement of unit costs can improve comparability, transferability, and generalizability of study findings.
Topics: Humans; Neoplasms; Exome Sequencing; Cost-Benefit Analysis; Chromosome Mapping; Rare Diseases; Genomics
PubMed: 36939042
DOI: 10.1016/j.gim.2023.100829 -
Comprehensive Psychiatry Aug 2024Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there...
BACKGROUND
Trichotillomania (TTM) and excoriation disorder (ED) are impairing obsessive-compulsive related disorders that are common in the general population and for which there are no clear first-line medications, highlighting the need to better understand the underlying biology of these disorders to inform treatments. Given the importance of genetics in obsessive-compulsive disorder (OCD), evaluating genetic factors underlying TTM and ED may advance knowledge about the pathophysiology of these body-focused repetitive behaviors.
AIM
In this systematic review, we summarize the available evidence on the genetics of TTM and ED and highlight gaps in the field warranting further research.
METHOD
We systematically searched Embase, PsycInfo, PubMed, Medline, Scopus, and Web of Science for original studies in genetic epidemiology (family or twin studies) and molecular genetics (candidate gene and genome-wide) published up to June 2023.
RESULTS
Of the 3536 records identified, 109 studies were included in this review. These studies indicated that genetic factors play an important role in the development of TTM and ED, some of which may be shared across the OCD spectrum, but there are no known high-confidence specific genetic risk factors for either TTM or ED.
CONCLUSIONS
Our review underscores the need for additional genome-wide research conducted on the genetics of TTM and ED, for instance, genome-wide association and whole-genome/whole-exome DNA sequencing studies. Recent advances in genomics have led to the discovery of risk genes in several psychiatric disorders, including related conditions such as OCD, but to date, TTM and ED have remained understudied.
Topics: Humans; Trichotillomania; Obsessive-Compulsive Disorder; Genome-Wide Association Study; Excoriation Disorder
PubMed: 38833896
DOI: 10.1016/j.comppsych.2024.152506 -
Clinical Infectious Diseases : An... Sep 2022Rare cases of thrombosis and thrombocytopenia (thrombosis with thrombocytopenia syndrome [TTS]) have been associated with 2 coronavirus disease 2019 adenovirus vector... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rare cases of thrombosis and thrombocytopenia (thrombosis with thrombocytopenia syndrome [TTS]) have been associated with 2 coronavirus disease 2019 adenovirus vector vaccines: the ChAdOx1 nCoV-19 Vaxzevria vaccine (Oxford/AstraZeneca) and the JNJ-7836735 Johnson & Johnson vaccine (Janssen). It is unknown if TTS is a class-mediated effect of adenovirus-based vaccines or if it could worsen known hypercoagulable states. Since most cases of TTS happen in women of childbearing age, pregnancy is a crucial risk factor to assess. Understanding these risks is important for advising vaccine recipients and future adenovirus vector vaccine development.
METHODS
To explore the potential associations of adenovirus-based vaccine components with symptoms of TTS in the general clinical trial population and in pregnant women in clinical trials, we conducted a systematic review and meta-analysis of adenovirus-based vector vaccines to document cases of thrombocytopenia, coagulopathy, and or pregnancy from 1 January 1966 to 9 August 2021.
RESULTS
We found 167 articles from 159 studies of adenovirus vector-based vaccines, 123 of which targeted infectious diseases. In the general population, 20 studies reported an event of thrombocytopenia and 20 studies indicated some coagulopathy. Among pregnant women, of the 28 studies that reported a total of 1731 pregnant women, thrombocytopenia or coagulopathy were not reported.
CONCLUSIONS
In this systematic review and meta-analysis, there was no class-wide effect of adenovirus vector vaccines toward thrombocytopenia or coagulopathy events in the general population or in pregnant women.
Topics: Adenoviridae; Adenovirus Vaccines; COVID-19; ChAdOx1 nCoV-19; Female; Humans; Pregnancy; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 35134164
DOI: 10.1093/cid/ciac080 -
World Journal of Pediatric Surgery 2022Previous studies have suggested an association between vascular endothelial growth factor A () rs3025039 polymorphism and biliary atresia (BA). However, this conclusion... (Review)
Review
BACKGROUND
Previous studies have suggested an association between vascular endothelial growth factor A () rs3025039 polymorphism and biliary atresia (BA). However, this conclusion is controversial and there is no published pooled evidence of this association.
METHODS
This study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews). A thorough search was performed on databases including PubMed, Embase, and Chinese Biomedical Database up to August 2020. This study included 846 cases of BA and 2821 controls concerning rs3025039 polymorphism. We selected relevant studies based on the following inclusion criteria: (1) the study design was case-control and cohort and (2) the patients carried standard clinical diagnoses of BA, etc. The exclusion criteria were as follows: (1) patients with other related diseases, (2) lack of requisite information and (3) duplicate data. The OR (odd ratio) and the corresponding 95% CI (confidence interval) were calculated to estimate the association.
RESULTS
This study on rs3025039 polymorphism in the Chinese population included 846 cases and 2821 controls. The results showed that there was no significant association between rs3025039 and susceptibility to BA under four genetic models. The results of the subgroup analysis were similar to the overall results.
CONCLUSIONS
This meta-analysis shows that rs3025039 was not associated with susceptibility to BA in the Chinese population. Further validation may entail additional research.
PROSPERO REGISTRATION NUMBER
CRD42020203812.
PubMed: 36474631
DOI: 10.1136/wjps-2021-000344 -
Journal of Psychiatric Research Jul 2023Obesity has been associated with elevated risk of depression. If this association is causal, the increasing obesity prevalence might lead to worsening population mental... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVES
Obesity has been associated with elevated risk of depression. If this association is causal, the increasing obesity prevalence might lead to worsening population mental health, but the strength of the causal effect has not been systematically evaluated.
SUBJECTS/METHODS
The current study provides a systematic review and meta-analysis of studies examining associations between body mass index and depression using Mendelian randomization with multiple genetic variants as instruments for body mass index. We used this estimate to calculate the expected changes in prevalence of population psychological distress from the 1990s-2010s, which were compared with the empirically observed trends in psychological distress in the Health Survey for England (HSE) and U.S. National Health Interview Surveys (NHIS).
RESULTS
Meta-analysis of 8 Mendelian randomization studies indicated an OR = 1.33 higher depression risk associated with obesity (95% confidence interval 1.19, 1.48). Between 15% and 20% of the participants of HSE and NHIS reported at least moderate psychological distress. The increase of obesity prevalence from the 1990s-2010s in HSE and NHIS would have led to a 0.6 percentage-point increase in population psychological distress.
CONCLUSIONS
Mendelian randomization studies suggest that obesity is a causal risk factor for elevated risk of depression. The increasing obesity rates may have modestly increased the prevalence of depressive symptoms in the general population. Mendelian randomization relies on methodological assumptions that may not always hold, so other quasi-experimental methods are needed to confirm the current conclusions.
Topics: Humans; Depression; Mental Health; Mendelian Randomization Analysis; Risk Factors; Obesity; Body Mass Index; Genome-Wide Association Study
PubMed: 37207436
DOI: 10.1016/j.jpsychires.2023.05.034 -
The Japanese Dental Science Review Nov 2022Primary headache disorders (PHD), specifically migraine, are strongly associated with temporomandibular disorders (TMD), sharing some patterns of orofacial pain. Both... (Review)
Review
Primary headache disorders (PHD), specifically migraine, are strongly associated with temporomandibular disorders (TMD), sharing some patterns of orofacial pain. Both disorders have significant genetic contributions already studied. PRISMA guidelines were followed to conduct this systematic review, which comprehensively summarize and discuss the genetic overlap between TMD and PHD to aid future research in potential therapy targets. This review included eight original articles published between 2015 and 2020, written in English and related to either TMD and/or PHD. The genes simultaneously assessed in PHD and TMD studies were and was proved to play a critical role in TMD pathogenesis, as all studies have concluded about its impact on the occurrence of the disease, although no association with PHD was found. No proof on the impact of gene regulation on either TMD or PHD was found. The most robust results are concerning the gene, which is present in the genetic profile of both clinical conditions. This novel systematic review highlights not only the need for a clear understanding of the role of and genes in pain pathogenesis, but it also evaluates their potential as a promising therapeutic target to treat both pathologies.
PubMed: 35242249
DOI: 10.1016/j.jdsr.2022.02.002 -
Neuropathology and Applied Neurobiology Jun 2023Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is... (Meta-Analysis)
Meta-Analysis Review
AIMS
Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD.
METHODS
A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean/mean differences and 95% confidence intervals.
RESULTS
Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-/Dp140+/Dp71+, Dp427-/Dp140-/Dp71+ and Dp427-/Dp140-/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-/Dp140-/Dp71+ vs Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71- vs Dp427-/Dp140-/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively.
CONCLUSIONS
The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ.
Topics: Humans; Dystrophin; Muscular Dystrophy, Duchenne; Protein Isoforms; Intelligence
PubMed: 37312416
DOI: 10.1111/nan.12914 -
Andrology Mar 2021The impact of human papillomavirus (HPV) on male fertility and associated reproductive outcomes has not been clarified. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The impact of human papillomavirus (HPV) on male fertility and associated reproductive outcomes has not been clarified.
OBJECTIVES
To elucidate the prevalence of seminal HPV infection and assess the associated effects on seminal parameters, male infertility, and reproductive outcomes.
MATERIALS AND METHODS
A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. A search was performed using PubMed, MEDLINE, SCOPUS, and Cochrane databases. Studies published until November 2019 were included. HPV prevalence, risk of infertility, seminal parameters, and reproductive outcomes were evaluated among the general population and infertile men.
RESULTS
Fifty studies met the inclusion criteria. The prevalence of seminal HPV infection is significantly higher in infertile compared to the general population (20.9% versus 8.2%). A significant association between seminal HPV infection and male infertility (OR 3.30, 95% CI 1.87-5.84), even when adjusting for female infertility (OR 3.02, 95% CI = 2.11-4.33) was founded. In addition, HPV infection is related to a significant decrease in progressive motility (DM -10.35, IC -13.75, -6.96), a low sperm morphology score (DM -2.46, 95% CI -3.83, -1.08), and a significant increase in the sperm DNA fragmentation index (7.24, 95% CI 4.44.10.03) compared with HPV-negative patients. It was also observed an increased risk of miscarriage (OR 5.13, 95% CI 2.40,10.94), and a reduced chance of ongoing pregnancy (OR 0.33, IC 95% 0.13,0,82) in patients undergoing ART with seminal HPV infection.
DISCUSSION
Infertile men have a higher prevalence of seminal HPV infection compared to the general population, regardless of the HPV genotype detected.
CONCLUSIONS
HPV in semen may have an impact in sperm quality and reproductive outcomes. Additional well-designed studies are warranted to improve the quality of evidence.
Topics: Alphapapillomavirus; Condylomata Acuminata; Cross-Sectional Studies; Female; Humans; Infertility, Male; Male; Papillomavirus Infections; Pregnancy; Pregnancy Outcome; Reproduction; Semen; Sperm Motility
PubMed: 33220146
DOI: 10.1111/andr.12948 -
Journal of the Association For Research... Feb 2024To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
PURPOSE
To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
METHODS
After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS
The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS
The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
Topics: Humans; Tinnitus; Genome-Wide Association Study; Hearing; Hearing Loss, Sensorineural; Hyperacusis
PubMed: 38334885
DOI: 10.1007/s10162-024-00925-6