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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 -
Human Molecular Genetics Aug 2018We present a systematic review of genome-wide research on psychotic experience and negative symptom (PENS) traits in the community. We integrate these new findings, most...
We present a systematic review of genome-wide research on psychotic experience and negative symptom (PENS) traits in the community. We integrate these new findings, most of which have emerged over the last four years, with more established behaviour genetic and epidemiological research. The review includes the first genome-wide association studies of PENS, including a recent meta-analysis, and the first SNP heritability estimates. Sample sizes of <10 000 participants mean that no genome-wide significant variants have yet been replicated. Importantly, however, in the most recent and well-powered studies, polygenic risk score prediction and linkage disequilibrium (LD) score regression analyses show that all types of PENS share genetic influences with diagnosed schizophrenia and that negative symptom traits also share genetic influences with major depression. These genetic findings corroborate other evidence in supporting a link between PENS in the community and psychiatric conditions. Beyond the systematic review, we highlight recent work on gene-environment correlation, which appears to be a relevant process for psychotic experiences. Genes that influence risk factors such as tobacco use and stressful life events are likely to be harbouring 'hits' that also influence PENS. We argue for the acceptance of PENS within the mainstream, as heritable traits in the same vein as other sub-clinical psychopathology and personality styles such as neuroticism. While acknowledging some mixed findings, new evidence shows genetic overlap between PENS and psychiatric conditions. In sum, normal variations in adolescent and adult thinking styles, such as feeling paranoid, are heritable and show genetic associations with schizophrenia and major depression.
Topics: Adult; Affect; Bipolar Disorder; Depressive Disorder, Major; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Genotype; Humans; Linkage Disequilibrium; Male; Multifactorial Inheritance; Phenotype; Polymorphism, Single Nucleotide; Psychiatry; Psychometrics; Psychotic Disorders; Risk Factors; Schizophrenia
PubMed: 29741616
DOI: 10.1093/hmg/ddy157 -
BMC Cancer Jan 2022Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value...
BACKGROUND
Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors.
METHODS
We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement.
RESULTS
We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry.
CONCLUSIONS
Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.
Topics: Adult; Area Under Curve; Asian People; Case-Control Studies; Clinical Decision Rules; Colorectal Neoplasms; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; White People
PubMed: 35030997
DOI: 10.1186/s12885-021-09143-2 -
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 -
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 -
Journal of Occupational and... Feb 2011Acute mountain sickness (AMS) has become a significant environmental health issue as improvements in transportation, "environmental tourism," and resource development... (Review)
Review
OBJECTIVE
Acute mountain sickness (AMS) has become a significant environmental health issue as improvements in transportation, "environmental tourism," and resource development lure more people to the highlands. Whether there is a genetic contribution to AMS susceptibility is a central question in high-altitude medicine. This article provides a systematic review of the evidence supporting such an innate predisposition.
METHODS
Scientific literature databases were screened using the terms "acute mountain sickness/AMS" and "altitude illness" combined with the terms "DNA," "gene," "genetic," or "polymorphism."
RESULTS
Sixteen genes from a variety of pathways have been tested for association with AMS and variants in eight showed positive associations suggesting that AMS is an environmentally mediated polygenic disorder.
CONCLUSIONS
The data suggest that genotype contributes to capacity to rapidly and efficiently acclimatize to altitude; nevertheless, the mechanisms by which this occurs have yet to be elucidated.
Topics: Acclimatization; Acute Disease; Altitude Sickness; Blood Pressure; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Multifactorial Inheritance; Oxidative Stress; Oxygen Consumption; Polymorphism, Genetic; Pulmonary Ventilation; Regional Blood Flow
PubMed: 21270658
DOI: 10.1097/JOM.0b013e318206b112 -
Clinical and Translational Medicine Jan 2022
Meta-Analysis
Topics: Alcohol Drinking; Genetic Loci; Genome-Wide Association Study; Heroin; Humans; Methamphetamine; Multifactorial Inheritance
PubMed: 35075802
DOI: 10.1002/ctm2.659 -
Journal of Affective Disorders May 2022Understanding the genetic underpinnings of antidepressant treatment response in unipolar major depressive disorder (MDD) can be useful in identifying patients at risk... (Review)
Review
BACKGROUND
Understanding the genetic underpinnings of antidepressant treatment response in unipolar major depressive disorder (MDD) can be useful in identifying patients at risk for poor treatment response or treatment resistant depression. A polygenic risk score (PRS) is a useful tool to explore genetic liability of a complex trait such as antidepressant treatment response. Here, we review studies that use PRSs to examine genetic overlap between any trait and antidepressant treatment response in unipolar MDD.
METHODS
A systematic search of literature was conducted in PubMed, Embase, and PsycINFO. Our search included studies examining associations between PRSs of psychiatric as well as non-psychiatric traits and antidepressant treatment response in patients with unipolar MDD. A quality assessment of the included studies was performed.
RESULTS
In total, eleven articles were included which contained PRSs for 30 traits. Studies varied in sample size and endpoints used for antidepressant treatment response. Overall, PRSs for attention-deficit hyperactivity disorder, the personality trait openness, coronary artery disease, obesity, and stroke have been associated with antidepressant treatment response in patients with unipolar MDD.
LIMITATIONS
The endpoints used by included studies differed significantly, therefore it was not possible to perform a meta-analysis.
CONCLUSIONS
Associations between a PRS and antidepressant treatment response have been reported for a number of traits in patients with unipolar MDD. PRSs could be informative to predict antidepressant treatment response in this population, given advances in the field. Most importantly, there is a need for larger study cohorts and the use of standardized outcome measures.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Multifactorial Inheritance; Risk Factors
PubMed: 35151671
DOI: 10.1016/j.jad.2022.02.015 -
Biological Reviews of the Cambridge... Apr 2021Evolutionary convergence provides natural opportunities to investigate how, when, and why novel traits evolve. Many convergent traits are complex, highlighting the...
Evolutionary convergence provides natural opportunities to investigate how, when, and why novel traits evolve. Many convergent traits are complex, highlighting the importance of explicitly considering convergence at different levels of biological organization, or 'multi-level convergent evolution'. To investigate multi-level convergent evolution, we propose a holistic and hierarchical framework that emphasizes breaking down traits into several functional modules. We begin by identifying long-standing questions on the origins of complexity and the diverse evolutionary processes underlying phenotypic convergence to discuss how they can be addressed by examining convergent systems. We argue that bioluminescence, a complex trait that evolved dozens of times through either novel mechanisms or conserved toolkits, is particularly well suited for these studies. We present an updated estimate of at least 94 independent origins of bioluminescence across the tree of life, which we calculated by reviewing and summarizing all estimates of independent origins. Then, we use our framework to review the biology, chemistry, and evolution of bioluminescence, and for each biological level identify questions that arise from our systematic review. We focus on luminous organisms that use the shared luciferin substrates coelenterazine or vargulin to produce light because these organisms convergently evolved bioluminescent proteins that use the same luciferins to produce bioluminescence. Evolutionary convergence does not necessarily extend across biological levels, as exemplified by cases of conservation and disparity in biological functions, organs, cells, and molecules associated with bioluminescence systems. Investigating differences across bioluminescent organisms will address fundamental questions on predictability and contingency in convergent evolution. Lastly, we highlight unexplored areas of bioluminescence research and advances in sequencing and chemical techniques useful for developing bioluminescence as a model system for studying multi-level convergent evolution.
Topics: Biological Evolution; Multifactorial Inheritance; Phenotype
PubMed: 33306257
DOI: 10.1111/brv.12672 -
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