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International Journal of Molecular... Mar 2020Recent studies have led to considerable advances in the identification of genetic variants associated with type 1 and type 2 diabetes. An approach for converting genetic...
Recent studies have led to considerable advances in the identification of genetic variants associated with type 1 and type 2 diabetes. An approach for converting genetic data into a predictive measure of disease susceptibility is to add the risk effects of loci into a polygenic risk score. In order to summarize the recent findings, we conducted a systematic review of studies comparing the accuracy of polygenic risk scores developed during the last two decades. We selected 15 risk scores from three databases (Scopus, Web of Science and PubMed) enrolled in this systematic review. We identified three polygenic risk scores that discriminate between type 1 diabetes patients and healthy people, one that discriminate between type 1 and type 2 diabetes, two that discriminate between type 1 and monogenic diabetes and nine polygenic risk scores that discriminate between type 2 diabetes patients and healthy people. Prediction accuracy of polygenic risk scores was assessed by comparing the area under the curve. The actual benefits, potential obstacles and possible solutions for the implementation of polygenic risk scores in clinical practice were also discussed. Develop strategies to establish the clinical validity of polygenic risk scores by creating a framework for the interpretation of findings and their translation into actual evidence, are the way to demonstrate their utility in medical practice.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; Multifactorial Inheritance
PubMed: 32131491
DOI: 10.3390/ijms21051703 -
Molecular Psychiatry Aug 2020Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by...
Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene-environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case-control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.
Topics: DNA Methylation; Epigenesis, Genetic; Gene-Environment Interaction; Histones; Humans; MicroRNAs; Psychotic Disorders; Schizophrenia
PubMed: 31907379
DOI: 10.1038/s41380-019-0601-3 -
Seminars in Neurology Feb 2020Meniere's disease (MD) is a set of uncommon disorders with core phenotype of tinnitus, episodic vertigo, and sensorineural hearing loss. MD shows a genetic...
Meniere's disease (MD) is a set of uncommon disorders with core phenotype of tinnitus, episodic vertigo, and sensorineural hearing loss. MD shows a genetic predisposition and a family history is found in 10% cases, with an autosomal dominant inheritance pattern. It is a multifactorial condition whose onset and development are triggered by the combined effect of genetic and environmental factors. Histopathological studies have associated MD with the accumulation of endolymph in the cochlea and the vestibular organs. However, endolymphatic hydrops does not fully explain the persistence of tinnitus, hearing loss progression, or the frequency of vertigo attacks.There are several comorbidities associated with MD, such as migraine, anxiety, autoimmune, and autoinflammatory disorders, adding more complexity to the phenotype. This "extended phenotype" can make the diagnosis and clinical management more complex, but it could also lead to a better characterization, understanding, and treatment of MD patients.We have conducted a systematic review on MD to update current knowledge, focusing on its mechanisms, diagnosis, comorbidities, and practical management.
Topics: Gene-Environment Interaction; Humans; Meniere Disease
PubMed: 31887752
DOI: 10.1055/s-0039-3402065 -
Heritability of blood pressure traits in diverse populations: a systematic review and meta-analysis.Journal of Human Hypertension Nov 2019To understand the genetic architecture and make inferences about transmissible resemblance of systolic and diastolic blood pressure (SBP and DBP) traits in relatives,... (Meta-Analysis)
Meta-Analysis
To understand the genetic architecture and make inferences about transmissible resemblance of systolic and diastolic blood pressure (SBP and DBP) traits in relatives, the polygenic effect of individual alleles in terms of narrow heritability (h) is usually assessed. The heritability estimates for BP traits are population specific parameters with a wide range in different studies (6-68%), and there is no comprehensive evidence comparing its source(s) of heterogeneity. To fill the gap, this systematic review and meta-analysis study was carried out. Using MeSH terms, 647 records were detected through searching, "Pubmed," "Ebsco," "Web of Science," and "Scopus" databases. From these, 24 relevant full-text articles with 47 comparisons for final quantitative meta-analysis were included in our review over the five continents. The additive genetic effects of both traits showed a widespread distribution (h: 17-52%, h:19-41%). Different categories of transmissible resemblance for BP traits were explained by ethnicity; higher heritability was estimated in Europeans and Mexican Americans, while lower heritability was seen in the Middle Eastern, Asians, Africans, Latinos, Hispanics, and American Indians. Low heterogeneity of polygenic effects was seen for both traits in subgroups of the Middle East, Asians, Africans, and Latinos, Hispanics, American Indians. However, there was a substantial heterogeneity of h within European and Mexican American studies. Neither pedigree type nor other covariates explained the variance of additive genetic effects of BP traits in different ethnicities.
Topics: Blood Pressure; Ethnicity; Genetic Predisposition to Disease; Heredity; Humans; Hypertension; Multifactorial Inheritance; Pedigree; Phenotype; Racial Groups; Risk Factors
PubMed: 31551569
DOI: 10.1038/s41371-019-0253-4 -
Archives of Oral Biology Dec 2019To present a genetic and protein interaction analysis associated with dental caries.
OBJECTIVE
To present a genetic and protein interaction analysis associated with dental caries.
MATERIAL AND METHODS
The first step was to conduct a systematic literature review (SLR) through an electronic database search. Case-controls that reported associations between genes and dental caries were the main type of study design used as inclusion criteria, retrieved from the PubMed and the Virtual Health Library databases, comprising the chronological range from 1982 to 2017. The SLR was guided by PRISMA protocol and the methodological quality of the studies was established through Newcastle-Ottawa Scale (NOS). In the second step, the String Protein Interaction (SPI) approach was used to analyze protein interaction (by esyN software) and also the Ingenuity Pathway Analysis (IPA) to check biological pathways associated with dental caries genes.
RESULTS
A total of 51 articles were included to perform this SLR, describing a number of 27 genes associated with dental caries development. At the genetic level, 23 genes have at least one other gene with which they interact. The genes TUFT1, VDR, TFIP11, LTF, HLA-DRB1, MMP2, MMP3 and MUC5B were shown to be connected in interactive networks by at least 10 other genes.
CONCLUSION
It is essential to apprehend the multifactorial pattern of inheritance in human disease. This study presents pathways which may be directly correlated with several dental caries phenotype and this contributes to a better understanding of this disease, opening up a wider range of biotechnology options for its effective control in the future.
Topics: Case-Control Studies; Dental Caries; Genetic Predisposition to Disease; Humans; Phenotype; Proteins
PubMed: 31476523
DOI: 10.1016/j.archoralbio.2019.104522 -
Psychiatric Genetics Oct 2019There are substantial differences, or variation, between humans in aggression, with its molecular genetic basis mostly unknown. This review summarizes knowledge on the...
There are substantial differences, or variation, between humans in aggression, with its molecular genetic basis mostly unknown. This review summarizes knowledge on the genetic contribution to variation in aggression with the following three foci: (1) a comprehensive overview of reviews on the genetics of human aggression, (2) a systematic review of genome-wide association studies (GWASs), and (3) an automated tool for the selection of literature based on supervised machine learning. The phenotype definition 'aggression' (or 'aggressive behaviour', or 'aggression-related traits') included anger, antisocial behaviour, conduct disorder, and oppositional defiant disorder. The literature search was performed in multiple databases, manually and using a novel automated selection tool, resulting in 18 reviews and 17 GWASs of aggression. Heritability estimates of aggression in children and adults are around 50%, with relatively small fluctuations around this estimate. In 17 GWASs, 817 variants were reported as suggestive (P ≤ 1.0E), including 10 significant associations (P ≤ 5.0E). Nominal associations (P ≤ 1E) were found in gene-based tests for genes involved in immune, endocrine, and nervous systems. Associations were not replicated across GWASs. A complete list of variants and their position in genes and chromosomes are available online. The automated literature search tool produced literature not found by regular search strategies. Aggression in humans is heritable, but its genetic basis remains to be uncovered. No sufficiently large GWASs have been carried out yet. With increases in sample size, we expect aggression to behave like other complex human traits for which GWAS has been successful.
Topics: Adult; Aggression; Antisocial Personality Disorder; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Child; Conduct Disorder; Environment; Epigenomics; Genome-Wide Association Study; Genomics; Humans; Multifactorial Inheritance; Phenotype; Supervised Machine Learning
PubMed: 31464998
DOI: 10.1097/YPG.0000000000000239