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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 -
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 -
Evolution; International Journal of... Dec 2021An evolutionary model for sex differences in disease risk posits that alleles conferring higher risk in one sex may be protective in the other. These sexually...
An evolutionary model for sex differences in disease risk posits that alleles conferring higher risk in one sex may be protective in the other. These sexually antagonistic (SA) alleles are predicted to be maintained at frequencies higher than expected under purifying selection against unconditionally deleterious alleles, but there are apparently no examples in humans. Discipline-specific terminology, rather than a genuine lack of such alleles, could explain this disparity. We undertook a two-stage review of evidence for SA polymorphisms in humans using search terms from (i) evolutionary biology and (ii) biomedicine. Although the first stage returned no eligible studies, the second revealed 51 genes with sex-opposite effects; 22 increased disease risk or severity in one sex but protected the other. Those with net positive effects occurred at higher frequencies. None were referred to as SA. Our review reveals significant communication barriers to fields as a result of discipline-specific terminology.
Topics: Alleles; Biological Evolution; Female; Humans; Male; Multifactorial Inheritance; Polymorphism, Genetic; Selection, Genetic
PubMed: 34723381
DOI: 10.1111/evo.14394