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Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
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 -
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 -
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 -
Viruses Jun 2023Norovirus is a common cause of sporadic cases and outbreaks of gastroenteritis worldwide, although its prevalence and the dominant genotypes responsible for... (Meta-Analysis)
Meta-Analysis
Norovirus is a common cause of sporadic cases and outbreaks of gastroenteritis worldwide, although its prevalence and the dominant genotypes responsible for gastroenteritis outbreaks remain obscure. A systematic review was conducted on norovirus infection in China between January 2009 and March 2021. A meta-analysis and beta-binomial regression model were used to explore the epidemiological and clinical characteristics of norovirus infection and the potential factors contributing to the attack rate of the norovirus outbreaks, respectively. A total of 1132 articles with 155,865 confirmed cases were included, with a pooled positive test rate of 11.54% among 991,786 patients with acute diarrhea and a pooled attack rate of 6.73% in 500 norovirus outbreaks. GII.4 was the predominant genotype in both the etiological surveillance and outbreaks, followed by GII.3 in the etiological surveillance, and GII.17 in the outbreaks, with the proportion of recombinant genotypes increasing in recent years. A higher attack rate in the norovirus outbreaks was associated with age group (older adults), settings (nurseries, primary schools, etc.) and region (North China). The nation-wide pooled positive rate in the etiological surveillance of norovirus is lower than elsewhere in the global population, while the dominant genotypes are similar in both the etiological surveillance and the outbreak investigations. This study contributes to the understanding of norovirus infection with different genotypes in China. The prevention and control of norovirus outbreaks during the cold season should be intensified, with special attention paid to and enhanced surveillance performed in nurseries, schools and nursing homes from November to March.
Topics: Humans; Aged; Prevalence; Phylogeny; Disease Outbreaks; Genotype; Gastroenteritis; Caliciviridae Infections; China; Norovirus
PubMed: 37376635
DOI: 10.3390/v15061336 -
Journal of Medical Internet Research Dec 2021The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward... (Review)
Review
BACKGROUND
The emergence of genetic and genomic sequencing approaches for pediatric patients has raised questions about the genomic health literacy levels, attitudes toward receiving genomic information, and use of this information to inform treatment decisions by pediatric patients and their parents. However, the methods to educate pediatric patients and their parents about genomic concepts through digital health interventions have not been well-established.
OBJECTIVE
The primary objective of this scoping review is to investigate the current levels of genomic health literacy and the attitudes toward receiving genomic information among pediatric patients and their parents. The secondary aim is to investigate patient education interventions that aim to measure and increase genomic health literacy among pediatric patients and their parents. The findings from this review will be used to inform future digital health interventions for patient education.
METHODS
A scoping review using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and protocols was completed using the following databases: MEDLINE, Embase, CINAHL, and Scopus. Our search strategy included genomic information inclusive of all genetic and genomic terms, pediatrics, and patient education. Inclusion criteria included the following: the study included genetic, genomic, or a combination of genetic and genomic information; the study population was pediatric (children and adolescents <18 years) and parents of patients with pediatric illnesses or only parents of patients with pediatric illnesses; the study included an assessment of the knowledge, attitudes, and intervention regarding genomic information; the study was conducted in the last 12 years between 2008 and 2020; and the study was in the English language. Descriptive data regarding study design, methodology, disease population, and key findings were extracted. All the findings were collated, categorized, and reported thematically.
RESULTS
Of the 4618 studies, 14 studies (n=6, 43% qualitative, n=6, 43% mixed methods, and n=2, 14% quantitative) were included. Key findings were based on the following 6 themes: knowledge of genomic concepts, use of the internet and social media for genomic information, use of genomic information for decision-making, hopes and attitudes toward receiving genomic information, experiences with genetic counseling, and interventions to improve genomic knowledge.
CONCLUSIONS
This review identified that older age is related to the capacity of understanding genomic concepts, increased genomic health literacy levels, and the perceived ability to participate in decision-making related to genomic information. In addition, internet-searching plays a major role in obtaining genomic information and filling gaps in communication with health care providers. However, little is known about the capacity of pediatric patients and their parents to understand genomic information and make informed decisions based on the genomic information obtained. More research is required to inform digital health interventions and to leverage the leading best practices to educate these genomic concepts.
Topics: Adolescent; Aged; Child; Communication; Genomics; Health Literacy; Humans; Parents; Pediatrics
PubMed: 34951592
DOI: 10.2196/26684 -
International Journal of Molecular... May 2023Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents... (Meta-Analysis)
Meta-Analysis Review
Breast cancer continues to be the leading cause of death in women worldwide. Mammography, which is the current gold standard technique used to diagnose it, presents strong limitations in early ages where breast cancer is much more aggressive and fatal. MiRNAs present in numerous body fluids might represent a new line of research in breast cancer biomarkers, especially oncomiRNAs, known to play an important role in the suppression and development of neoplasms. The aim of this systematic review and meta-analysis was to evaluate dysregulated miRNA biomarkers and their diagnostic accuracy in breast cancer. Two independent researchers reviewed the included studies according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A protocol for this review was registered in PROSPERO with the registration number "CRD42021256338". Observational case-control-based studies analyzing concentrations of microRNAs which have been published within the last 10 years were selected, and the concentrations of miRNAs in women with breast cancer and healthy controls were analyzed. Random-effects meta-analyses of miR-155 were performed on the studies which provided enough data to calculate diagnostic odds ratios. We determined that 34 microRNAs were substantially dysregulated and could be considered biomarkers of breast cancer. Individually, miR-155 provided better diagnostic results than mammography on average. However, when several miRNAs are used to screen, forming a panel, sensitivity and specificity rates improve, and they can be associated with classic biomarkers such us CA-125 or CEA. Based on the results of our meta-analysis, miR-155 might be a promising diagnostic biomarker for this patient population.
Topics: Humans; Female; MicroRNAs; Biomarkers, Tumor; Breast Neoplasms; Breast; Sensitivity and Specificity
PubMed: 37175974
DOI: 10.3390/ijms24098270 -
Nutrients Jun 2023Diabetes and obesity are chronic diseases that are a burden to low- and middle-income countries. We conducted this systematic review to understand gene-diet interactions... (Review)
Review
Diabetes and obesity are chronic diseases that are a burden to low- and middle-income countries. We conducted this systematic review to understand gene-diet interactions affecting the Southeast Asian population's risk of obesity and diabetes. The literature search was performed on Google Scholar and MEDLINE (PubMed) search engines independently by four reviewers who evaluated the eligibility of articles based on inclusion criteria. Out of 19,031 articles, 20 articles examining gene-diet interactions on obesity and/or diabetes-related traits met the inclusion criteria. Three (Malaysia, Indonesia, and Singapore) out of eleven Association of Southeast Asian Nations (ASEAN) countries have conducted studies on gene-diet interactions on obesity and diabetes. From the 20 selected articles, the most common interactions were observed between macronutrients and genetic risk score (GRS) on metabolic disease-related traits in the Malay, Chinese, and Indian ethnicities. Overall, we identified 29 significant gene-diet interactions in the Southeast Asian population. The results of this systematic review demonstrate ethnic-specific gene-nutrient interactions on metabolic-disease-related traits in the Southeast Asian population. This is the first systematic review to explore gene-diet interactions on obesity and diabetes in the Southeast Asian population and further research using larger sample sizes is required for better understanding and framing nutrigenetic approaches for personalized nutrition.
Topics: Humans; Asia, Southeastern; Diet; Obesity; Singapore; Southeast Asian People; Diabetes Mellitus
PubMed: 37447274
DOI: 10.3390/nu15132948 -
Evolution, Medicine, and Public Health 2021Social scientists have long understood race to be a social category invented to justify slavery and evolutionary biologists know the socially constructed racial... (Review)
Review
Social scientists have long understood race to be a social category invented to justify slavery and evolutionary biologists know the socially constructed racial categories do not align with our biological understanding of genetic variation. The completion of the Human Genome Project in 2003 confirmed humans are 99.9% identical at the DNA level and there is no genetic basis for race. A systematic review of the PubMed medical literature published since 2003 was conducted to assess the use of African ancestry to denote study populations in genetic studies categorized as clinical trials, to examine the stated rationale for its use and to assess the use of evolutionary principles to explain human genetic diversity. We searched for papers that included the terms 'African', 'African American' or 'Black' in studies of behavior (20 papers), physiological responses, the pharmacokinetics of drugs and/or disease associations (62 papers), and as a genetic category in studies, including the examination of genotypes associated with life stress, pain, stuttering and drug clearance (126 papers). Of these, we identified 74 studies in which self-reported race alone or in combination with admixture mapping was used to define the study population. However, none of these studies provided a genetic explanation for the use of the self-identified race as a genetic category and only seven proffered evolutionary explanations of their data. The concept of continuous genetic variation was not clearly articulated in any of these papers, presumably due to the paucity of evolutionary science in the college and medical school curricula.
PubMed: 34815885
DOI: 10.1093/emph/eoab018 -
British Journal of Cancer Jun 2023Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS.
METHODS
We conducted a systematic review to identify CS cases to create a retrospective cohort. We tested genotype-phenotype correlations and calculated cumulative incidence and hazard rates (HR) for cancer and cancer-free death, standardised incidence rates (SIR) and survival after cancer.
RESULTS
This study includes 234 publications reporting 621 patients from 35 countries. Over nine percent had cancer, including rhabdomyosarcoma, bladder, and neuroblastoma. The rate of cancer and death associated with p.Gly12Ser were lower when compared to all other variants (P < 0.05). Higher mortality for p.Gly12Cys, p.Gly12Asp, p.Gly12Val and p.Gly60Val and higher malignancy rate for p.Gly12Ala were confirmed (P < 0.05). Cumulative incidence by age 20 was 13% (cancer) and 11% (cancer-free death). HR (death) was 3-4% until age 3. Statistically significant SIRs were found for rhabdomyosarcoma (SIR = 1240), bladder (SIR = 1971), and neuroblastoma (SIR = 60). Survival after cancer appeared reduced.
CONCLUSIONS
This is the largest investigation of cancer in CS to date. The high incidence and SIR values found to highlight the need for rigorous surveillance and evidence-based guidelines for this high-risk population.
Topics: Humans; Costello Syndrome; Retrospective Studies; Genotype; Rhabdomyosarcoma; Neuroblastoma
PubMed: 36966234
DOI: 10.1038/s41416-023-02229-7