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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 -
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 -
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 -
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 -
Brain Imaging and Behavior Jun 2019Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified...
Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.
Topics: Bipolar Disorder; Brain; Cognition; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Magnetic Resonance Imaging; Male; Multifactorial Inheritance; Psychotic Disorders; Risk Factors; Schizophrenia
PubMed: 29748770
DOI: 10.1007/s11682-018-9879-z -
American Journal of Medical Genetics.... Jul 2024Debates about the prospective clinical use of polygenic risk scores (PRS) have grown considerably in the last years. The potential benefits of PRS to improve patient... (Review)
Review
Debates about the prospective clinical use of polygenic risk scores (PRS) have grown considerably in the last years. The potential benefits of PRS to improve patient care at individual and population levels have been extensively underlined. Nonetheless, the use of PRS in clinical contexts presents a number of unresolved ethical challenges and consequent normative gaps that hinder their optimal implementation. Here, we conducted a systematic review of reasons of the normative literature discussing ethical issues and moral arguments related to the use of PRS for the prevention and treatment of common complex diseases. In total, we have included and analyzed 34 records, spanning from 2013 to 2023. The findings have been organized in three major themes: in the first theme, we consider the potential harms of PRS to individuals and their kin. In the theme "Threats to health equity," we consider ethical concerns of social relevance, with a focus on justice issues. Finally, the theme "Towards best practices" collects a series of research priorities and provisional recommendations to be considered for an optimal clinical translation of PRS. We conclude that the use of PRS in clinical care reinvigorates old debates in matters of health justice; however, open questions, regarding best practices in clinical counseling, suggest that the ethical considerations applicable in monogenic settings will not be sufficient to face PRS emerging challenges.
Topics: Humans; Multifactorial Inheritance; Genetic Predisposition to Disease; Morals; Genetic Testing; Risk Assessment; Genetic Counseling; Risk Factors; Genetic Risk Score
PubMed: 38450933
DOI: 10.1002/ajmg.a.63584 -
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 -
Frontiers in Psychiatry 2021Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the...
Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the role of copy number variants (generally deletions) and certain alleles of common single nucleotide polymorphisms in the pathogenesis of schizophrenia. This disorder predominantly follows the polygenic inheritance model. Schizophrenia has also been linked with various alterations in the transcript and protein content of the brain tissue. Recent studies indicate that alterations in non-coding RNAs (ncRNAs) signature underlie a proportion of this dysregulation. High throughput microarray investigations have demonstrated momentous alterations in the expression of long non-coding RNAs (lncRNA) and microRNAs (miRNAs) in the circulation or post-mortem brain tissues of patients with schizophrenia compared with control samples. While Gomafu, PINT, GAS5, TCONS_l2_00021339, IFNG-AS1, FAS-AS1, PVT1, and TUG1 are among down-regulated lncRNAs in schizophrenia, MEG3, THRIL, HOXA-AS2, Linc-ROR, SPRY4-IT1, UCA1, and MALAT1 have been up-regulated in these patients. Moreover, several miRNAs, such as miR-30e, miR-130b, hsa-miR-130b, miR-193a-3p, hsa-miR-193a-3p, hsa-miR-181b, hsa-miR-34a, hsa-miR-346, and hsa-miR-7 have been shown to be dysregulated in blood or brain samples of patients with schizophrenia. Dysregulation of these transcripts in schizophrenia not only provides insight into the pathogenic processes of this disorder, it also suggests these transcripts could serve as diagnostic markers for schizophrenia. In the present paper, we explore the changes in the expression of miRNAs and lncRNAs in patients with schizophrenia.
PubMed: 34220567
DOI: 10.3389/fpsyt.2021.640463 -
Postepy Biochemii Sep 2022This study aims to present the current state of knowledge on the DNA-based prediction of human externally visible characteristics of an unknown person based on the crime...
This study aims to present the current state of knowledge on the DNA-based prediction of human externally visible characteristics of an unknown person based on the crime scene biological material left behind. This DNA sample is referred to as a “biological witness” and the procedure itself is called forensic DNA phenotyping (FDP). The analytic part of this work is based on scholarly articles published between 2015 and 2021. The electronic search of relevant references was conducted according to the PRISMA methodology in March 2021 at EBSCO Discovery Service (EDS) at the Adam Mickiewicz University library and Google Scholar. The molecular basis of FDP, DNA markers used to predict sex, age, biogeographic origin and externally visible traits such as pigmentation (skin, eye and hair colour), hair morphology, facial morphology, presence of freckles, body height, body weight (obesity), male pattern baldness and myopia were described. Furthermore, methodological difficulties resulting from the polygenic inheritance of the studied traits, as well as social and ethical problems accompanying forensic DNA phenotyping were discussed. Finally, key themes for future research related to forensic DNA phenotyping were outlined.
Topics: Female; Humans; Male; DNA; Eye Color; Forensic Genetics; Hair Color; Phenotype
PubMed: 36317992
DOI: 10.18388/pb.2021_449