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Neuron Feb 2014Major depression is the commonest psychiatric disorder and in the U.S. has the greatest impact of all biomedical diseases on disability. Here we review evidence of the... (Review)
Review
Major depression is the commonest psychiatric disorder and in the U.S. has the greatest impact of all biomedical diseases on disability. Here we review evidence of the genetic contribution to disease susceptibility and the current state of molecular approaches. Genome-wide association and linkage results provide constraints on the allele frequencies and effect sizes of susceptibility loci, which we use to interpret the voluminous candidate gene literature. We consider evidence for the genetic heterogeneity of the disorder and the likelihood that subtypes exist that represent more genetically homogenous conditions than have hitherto been analyzed.
Topics: Depressive Disorder, Major; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Genetic Variation; Humans; Molecular Epidemiology
PubMed: 24507187
DOI: 10.1016/j.neuron.2014.01.027 -
Australian Dental Journal Mar 2015This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic... (Review)
Review
This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic aspects of various dental factors affecting dental caries. The PubMed database was searched for articles with keywords 'caries', 'genetics', 'taste', 'diet' and 'twins'. This was followed by extensive handsearching using reference lists from relevant articles. The post-genomic era will present many opportunities for improvement in oral health care but will also present a multitude of challenges. We can conclude from the literature that genes have a role to play in dental caries; however, both environmental and genetic factors have been implicated in the aetiology of caries. Additional studies will have to be conducted to replicate the findings in a different population. Identification of genetic risk factors will help screen and identify susceptible patients to better understand the contribution of genes in caries aetiopathogenesis. Information derived from these diverse studies will provide new tools to target individuals and/or populations for a more efficient and effective implementation of newer preventive measures and diagnostic and novel therapeutic approaches in the management of this disease.
Topics: Dental Caries; Dental Caries Susceptibility; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Risk Factors
PubMed: 25721273
DOI: 10.1111/adj.12262 -
Blood Mar 2023
Topics: Humans; Genetic Predisposition to Disease; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Immunity; HLA-E Antigens
PubMed: 36995704
DOI: 10.1182/blood.2022019180 -
Current Opinion in Oncology Mar 2019Genetic mosaicism is the presence of a somatic mutation in a subset of cells that differs from the inherited germline genome. Detectable genetic mosaicism is attractive... (Review)
Review
PURPOSE OF REVIEW
Genetic mosaicism is the presence of a somatic mutation in a subset of cells that differs from the inherited germline genome. Detectable genetic mosaicism is attractive as a potential early biomarker for cancer risk because of its established relationship with aging, introduction of potentially deleterious mutations, and clonal selection and expansion of mutated cells. The aim of this review is to survey shared risk factors associated with genetic mosaicism, aging and cancer risk.
RECENT FINDINGS
Studies have associated aging, cigarette smoking and several genetic susceptibility loci with increased risk of acquiring genetic mosaicism. Genetic mosaicism has also been associated with numerous outcomes including cancer risk and cancer mortality; however, the level of evidence supporting these associations varies considerably.
SUMMARY
Ample evidence exists for shared risk factors for genetic mosaicism and cancer risk as well as abundant support linking genetic mosaicism in leukocytes to hematologic malignancies. The relationship between genetic mosaicism in circulating leukocytes and solid malignancies remains an active area of research.
Topics: Age Factors; Aging; Genetic Predisposition to Disease; Humans; Mosaicism; Neoplasms
PubMed: 30585859
DOI: 10.1097/CCO.0000000000000500 -
Reumatologia Clinica 2015Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have... (Review)
Review
Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA.
Topics: Gene-Environment Interaction; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Osteoarthritis
PubMed: 24992825
DOI: 10.1016/j.reuma.2014.05.004 -
Oncotarget Mar 2023
Topics: Child; Humans; Leukemia; Genetic Predisposition to Disease
PubMed: 36913308
DOI: 10.18632/oncotarget.28371 -
Current Opinion in Lipidology Apr 2016Cerebrovascular disease (CeVD) remains a major cause of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the... (Review)
Review
PURPOSE OF REVIEW
Cerebrovascular disease (CeVD) remains a major cause of death and a leading cause of disability worldwide. CeVD is a complex and multifactorial disease caused by the interaction of vascular risk factors, environment, and genetic factors. In the present article, we discussed genetic susceptibility to CeVD, with particular emphasis on genetic studies of the associations between lipid traits and CeVD.
RECENT FINDINGS
Several animal and clinical studies clearly defined genetic predisposition to atherosclerosis and CeVD, and particularly to ischemic stroke. Recent evidence has shown that traditional vascular risk factors explain only a small proportion of variance in atherosclerosis, suggesting that additional nontraditional factors and novel genetic determinants impact CeVD. With the help of genome-wide technology, novel genetic variants have been implicated in CeVD and lipid metabolism such as those in protein convertase subtilisin/kexin type 9 (PCSK9) gene in stroke and familial hypercholesterolemia. These studies are important as they contribute to our understanding of the genetic mechanisms underlying CeVD and to developing more effective CeVD prevention strategies.
SUMMARY
CeVD is a complex and multifactorial disease and genetics likely plays an important role in its pathogenesis. The gene-gene and gene-environment interactions of genes involved in biology of vascular disease, including the lipid metabolism are important factors for individual susceptibility to CeVD. Accounting for individual variation in genes, environment and lifestyle will bring us closer to precision medicine, which is an emerging and recently introduced new approach for disease treatment and prevention in clinical practice.
Topics: Animals; Cerebrovascular Disorders; Dyslipidemias; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lipid Metabolism
PubMed: 26959706
DOI: 10.1097/MOL.0000000000000275 -
PLoS Neglected Tropical Diseases Apr 2020Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the...
Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify 'at-risk' individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future.
Topics: Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Immunologic Factors; Male; Mycetoma; Polymorphism, Genetic; Risk Factors
PubMed: 32352976
DOI: 10.1371/journal.pntd.0008053 -
Magyar Onkologia Mar 2020The majority of haematological malignancies represent sporadic diseases, but hereditary entities with predisposing genetic alterations have also been described. Diseases... (Review)
Review
The majority of haematological malignancies represent sporadic diseases, but hereditary entities with predisposing genetic alterations have also been described. Diseases of the myeloid and lymphoid cell lineages with genetic predispositions are associated with heterogeneous clinical manifestations, with many symptoms being specific for certain cytogenetic and molecular aberrations. Apart from the myeloid predisposition syndromes with clear Mendelian inheritance patterns, cases with ambiguous predisposing factors are also known, but their role in hereditary leukemogenesis is still poorly understood. The presence of these genetic lesions is usually associated with an increased risk of familial malignancies and often leads to familial disease aggregation. Lymphoid malignancies often lack the disease-associated germline pathogenic variants, with their propensity to familial aggregation being most likely explained by their complex genotype serving as a hereditary base to many sporadic diseases. The heterogeneous clinical features and the large number of potentially affected genes tend to make the diagnosis of hereditary haematological malignancies difficult, however the elevated familial risk caused by predisposing genetic alterations underlines the importance of testing for individuals and families with genetic susceptibility.
Topics: Family Health; Genetic Predisposition to Disease; Hematologic Neoplasms; Humans; Mutation
PubMed: 32181762
DOI: No ID Found -
Clinical Microbiology and Infection :... Nov 2022During the past decades, studies on patients with severe viral infections have revealed rare inborn errors of immunity (IEIs) underlying these diseases. This has led to... (Review)
Review
BACKGROUND
During the past decades, studies on patients with severe viral infections have revealed rare inborn errors of immunity (IEIs) underlying these diseases. This has led to important new insights into the molecular genetics and immunological mechanisms governing susceptibility to viral infection in humans.
OBJECTIVES
Herein, the current knowledge on major IEIs predisposing to severe or chronic viral infections are described and discussed, and the clinical implications of these findings for individualized prophylaxis and treatment are outlined.
SOURCES
The review is based on a broad literature search, including relevant studies primarily based on patients, supported by experimental molecular models in vitro or in mice, to characterize the pathophysiological mechanism governing these disease conditions.
CONTENT
Current concepts and principles of genetic predisposition to viral infections in humans are described with a major focus on defects related to innate immune responses and new concepts of constitutive immune mechanisms. The topic therefore spans from seminal studies on the human genetics of herpesvirus infections in the central nervous system, severe influenza, and disease after vaccination with live attenuated viral vaccines, to genetic resistance to viral infection.
IMPLICATIONS
Past and present studies of patients with IEIs conferring vulnerability to viral infections have taught us important lessons on protective innate and adaptive antiviral immunity in humans. Such knowledge also has important clinical implications, allowing development of prophylactic and therapeutic solutions to prevent or dampen the clinical consequences of insufficient or dysregulated antiviral immunity in patients. Collectively, such measures are likely to improve patient management at an individualized level and help societies reduce the disease burden from viral infections.
Topics: Humans; Mice; Animals; Genetic Predisposition to Disease; Virus Diseases; Immunity, Innate; Influenza Vaccines; Antiviral Agents; Vaccines, Attenuated; Disease Susceptibility
PubMed: 35218976
DOI: 10.1016/j.cmi.2022.02.023