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Results for “Genetic causality”

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At least 559 records · Page 31Linked to original sources
PubMed2004

Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in 200 healthy Jordanians.

Thrombophilia is now considered a multi-causal condition, with interplay of acquired genetic risk factors. In order to estimate the frequency of the factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in the Jordanian population, we screened 200 healthy Jordanian individuals. 40% were females. Mean age was 32.1 years for males and 30.0 years for female participants. A PCR method detected 15.0% factor V Leiden (87% heterozygous, 13% homozygous), 2% prothrombin G20210A (100% heterozygous), and 24% MTHFR C677T (67% heterozygous, 33% homozygous). We conclude that the prevalence of factor V Leiden and MTHFR C677T is elevated in this population of Jordanians. However the incidence of G20210A is relatively low. Quantification of these genetic thrombosis risk factors in various populations will contribute to a better understanding of the interaction of genetic and environmental risk factors.

Adult↗
PubMed1991

[Psychological interpretation of organic diseases and psychoanalytic speculation on the past].

By using examples of psychotherapy applications the author critically analyzes a tendency of speculative psychoanalytical explanation of organic illnesses on the basis of the patient's biography. Typical clinical pictures are described. Probable causes of this tendency of speculation in a psychoanalytical manner are discussed. The author also refers to the tradition of speculative theories in psychoanalysis, the meaning of behavorism for psychoanalysis as well as the denial of hereditary-genetic factors. The imponderableness of the causal meaning of biographical events is demonstrated. Impulses for training are given.

Asthma↗
PubMed1979

Current concepts of the etiology of central nervous system malformations.

We have seen that what must be applied to dysmorphology is the doctrine of multifactorial causality, ie dysmorphogenetic events have both genetic and nongenetic etiologic components to varying degrees. Complicating matters is the extent to which there is etiologic and/or mechanistic heterogeneity (Fig. 1). This is nicely illustrated by the holoprosencephaly anomaly. In addition, there are numerous CNS malformations that have major single gene, chromosomal, or environmental initiating agents of malformation mechanisms. Still a mystery is the common neural tube malformations. It is now clear that the "multifactorial/threshold" model is an inadequate explanation of the observed data and until the etiologic heterogeneity of these malformations is clearly defined, our knowledge remains primarily empiric. A potential area of fruitful investigation is likely to be the identification of maternal genotypes which do not allow detoxification of potential environmental teratogens.

Central Nervous System↗
PubMed1993

Chaos, population biology, and epidemiology: some research implications.

In this article I aim to provide some feeling of the new paradigm of disease causation (chaos) as it applies to the field of population biology and epidemiology. A secondary objective is to show, with the aid of qualitative methods, how one can approach chaos in time-series data. The multifactorial stochastic paradigm of causation is contrasted with the new deterministic approach. This approach is embedded in the theory of nonlinear system dynamics. Chaos implies that randomness is intrinsic to a nonlinear deterministic system; this is true despite the extent of knowledge of the intervening causes and, ultimately, despite determinism. Three research avenues are discussed in depth from the standpoint of chaos theory. First, the topic of sporadic epidemics is dealt with. I argue that the space-time clustering of cases from a starting epidemic is due to a sudden and high increase of the contact rate beyond a threshold. Interaction rather than main effects and nonlinear rather than linear dynamics are involved. Second, the incubation period of disease is studied. I advocate that an individual-level deterministic process underlies Sartwell's model of the incubation period. This accounts for the robustness of the model vis-à-vis confounding variables. Third, monozygotic twinning is analyzed. Assumed by some to be a random process, monozygotic twinning proves to be dynamically different from dizygotic or single-maternity processes; its dynamics can actually be chaotic. Throughout the provided examples, the point is made that chancelike phenomena are primarily concerned with chaos theory. For biological problems showing recurrent inconsistencies by stochastic modeling, dynamic modeling should be envisaged. Inconsistencies can suggest that the relevant factors are out of the model and that they are related deterministically. Finally, spectral analysis and attractors in the phase space are presented; these tools can aid the population biologist in tracing out chaos from time-series data sets. Several time-series data sets are simulated according to a simple nonlinear difference equation that bears some relationship to the basics of the dynamics of infections in the population. I show how the series can be analyzed and interpreted. Much research remains to be carried out until the nonlinear effects of risk factors can be validated. The undertaking is worth the effort, as a new paradigm of causation is at stake.

Causality↗
PubMed1995

[Prenatal diagnosis of cutaneous genetic diseases by the study of fetal DNA].

There has been considerable progress in chromosome mapping and gene identification in several severe hereditary skin diseases, leading to changes in genetic counseling. It is now possible to propose antenatal diagnosis to couples at risk based on an analysis of foetal DNA from trophoblast biopsies performed as early as the 9th week of gestation. Antenatal can be made by direct analysis based on identifying the mutation known in the family at risk or on indirect analysis based on the linkage disequilibrium of the allele or alleles associated with the disease in the family at risk. This method has already been shown to be effective in recessive dystrophic bullous epidermolysis, lethal Herlitz's junctional bullous epidermolysis, bullous ichthyosiform hereditary erythroderma, von Recklinghausen's neurofibromatosis, tyrosinase negative oculocutaneous albinism, Gorlin's syndrome, anhidrotic ectodermic dysplasia and Menkes disease. These techniques will replace microscopic examination of ultrastructure in foetal skin biopsies performed at 20 weeks gestation. They can also be applied to diseases where the antenatal diagnosis now relies on enzyme function tests or DNA distribution. Improving genetic counselling in these diseases requires the identification of the implicated genes, identification of the causal mutations in the families at risk and development of genetic markers for these diseases.

DNA↗
PubMed1997

Molecular epidemiology of atherosclerosis.

It has been hypothesized that mutational events may be involved in the atherogenetic process and that at least a portion of atherosclerotic plaques may develop according to an initiation-promotion process of arterial smooth muscle cells, akin to benign tumors. We conducted a study to evaluate the occurrence of oxidative DNA damage and formation of DNA adducts in human atherosclerotic lesions and to assess the relationships of these promutagenic alterations with exposure to atherogenic risk factors. Pure DNA was extracted from the tunica media (composed mainly of smooth muscle cells) of abdominal aorta fragments taken at surgery from 85 patients suffering from severe atherosclerotic lesions. DNA adducts were detected by synchronous fluorescence spectrophotometry and 32P postlabeling after enrichment of adducts with either butanol or nuclease P1. 8-Hydroxy-2'-deoxyguanosine (8-OH-dG), a typical indicator of oxidative DNA damage, was measured by HPLC/electrochemical detection. A complete questionnaire reporting general, clinical, and laboratory characteristics was available for each patient. All 84 samples tested by 32P postlabeling were positive by displaying the presence of diagonal radioactive zones and up to 9 individual DNA adducts. Of 52 samples tested, 32 (61.5%) yielded typical positive signals at synchronous fluorescence spectrophotometry. All but one of 39 samples tested had very high levels of 8-OH-dG, thus showing a remarkable oxidative DNA damage. Statistically significant correlations were found between the levels of molecular biomarkers and atherogenic risk factors including age, number of currently smoked cigarettes, ratio of total-to-high density lipoprotein blood cholesterol, blood triglycerides, and blood pressure. The DNA alterations detected in our study may be only one component of the genetic basis of atherogenesis. Moreover, no causal role in the atherogenetic process can be inferred from our results. However, DNA alterations, including oxidative damage and adduction of reactive molecules of either endogenous or exogenous source, were systematically present in the smooth muscle cells of human atherosclerotic lesions and their intensity was significantly correlated with the occurrence of atherogenic risk factors in the patients studied.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2026

Ferroptosis as a mediator of gut microbiota-driven inflammatory bowel disease: Evidence from genetic analyses.

Gut microbiota dysbiosis is increasingly recognized as a contributor to inflammatory bowel disease (IBD), yet causal relationships and underlying mechanisms remain unclear. Ferroptosis, an iron-dependent form of regulated cell death, plays a key role in epithelial barrier damage and inflammation. This study aimed to determine whether specific gut microbial taxa are causally associated with IBD and whether ferroptosis-related genes mediate this association using Mendelian randomization (MR). Two-sample MR and mediation MR analyses were performed using genome-wide association study summary data from the FinnGen consortium (IBD), the genome-wide association study catalog (473 gut microbial taxa), and the deCODE database (ferroptosis-related genes). Instrumental variables were selected with thresholds of P&#x2005;<&#x2005;1&#x2005;&#xd7;&#x2005;10-6 for microbes and P&#x2005;<&#x2005;5&#x2005;&#xd7;&#x2005;10-8 for traits, and linkage disequilibrium clumping (r2&#x2005;<&#x2005;0.001) was applied. Twenty-three microbial taxa showed significant causal associations with IBD (e.g., Chromatiales, OR&#x2005;=&#x2005;0.51; Acetobacterales, OR&#x2005;=&#x2005;2.61). Several ferroptosis-related genes were linked to IBD risk (e.g., GPX4, STAT3, IDO1). Mediation MR revealed that genes such as MUC1, IDO1, and ADAM23 partially mediated microbial effects on IBD, with mediation proportions up to 7.6%. This study provides novel genetic evidence supporting a gut microbiota-ferroptosis-IBD axis. Ferroptosis-related pathways may partially mediate microbial effects on IBD pathogenesis and represent promising targets for future therapeutic interventions.

Ferroptosis↗
PubMed2026

The causal effect of family history of cardiovascular disease on erectile dysfunction: a randomized clinical study and Mendelian randomization study.

Erectile dysfunction (ED) is increasingly recognized as an early clinical marker of cardiovascular disease (CVD); however, the causal role of familial predisposition to CVD in ED development remains insufficiently defined. This study investigated whether genetic susceptibility associated with a parental history of CVD exerts a causal influence on ED risk, integrating clinical data with Mendelian randomization (MR) analysis. A cohort of 288 men who attended the Department of Andrology of Xiangya Hospital (Changsha, China) between June 2017 and June 2023 were recruited, comprising 223 patients with clinically confirmed ED and 65 controls. Detailed demographic, cardiovascular, and ED severity data were collected. Genetic variants associated with ED and parental CVD history were obtained from genome-wide association study (GWAS) summary statistics, and two-sample MR analyses were conducted to evaluate causal effects. Clinically, men with ED were significantly older, exhibited higher body mass index (BMI), and demonstrated lower testosterone levels compared with controls. A trend toward an association between family history of CVD and ED was observed. MR analyses provided robust evidence of causality, with paternal CVD history increasing ED risk and maternal CVD history exerting an even stronger effect. Sensitivity analyses confirmed the stability of these findings without evidence of pleiotropic bias. Collectively, these results indicate that familial genetic susceptibility to CVD independently contributes to the risk of ED. These findings underscore the clinical importance of incorporating family history into ED risk stratification and highlight the need for early screening and preventive strategies in men with a family history of CVD. Proactive management of this high-risk population may mitigate the future burden of ED and its cardiovascular sequelae.

Humans↗
PubMed1994

Growth areas in hypertension.

Essential hypertension is an arbitrarily defined disorder to which both environmental and genetic factors contribute. Identifying these factors is a difficult task because individually their contribution is relatively small and apparent causality may be the result of secondary changes or genetic drift. Associations between elevated blood pressure and genetic or phenotypic characteristics are insufficient therefore to demonstrate a cause and effect relationship. This conclusion requires that stringent criteria are met including the presence of the abnormality at or before the first manifestation of hypertension, co-segregation of the relevant gene, reversibility of hypertension when the abnormality is removed (at least during the early phases of hypertension) and failure of the abnormality to resolve with the correction of hypertension. It is proposed that these conditions constitute 'Koch's postulates' for defining the causes of elevated blood pressure.

Causality↗
PubMed2026

Genetics of sensory nutrition.

Sensory nutrition is an emerging research area that examines how chemosensory perception, particularly taste and smell, shapes dietary behaviours, nutritional status, and disease risk. Variation in how individuals perceive the same foods may help explain differences in diet quality and responsiveness to behavioural dietary interventions, yet chemosensory phenotypes are rarely measured at the population level. Genetic variation contributes to this perceptual diversity and provides a framework for investigating sensory determinants of diet using genomic approaches. This review summarises evidence linking chemosensory genetics to perception and dietary behaviours, and discusses applications for causal inference and for&#xa0;precision and personalised nutrition. Twin studies reveal moderate to high heritability for bitter taste traits, with more modest and phenotype-dependent estimates for sweetness, sourness, saltiness, fat-related traits, and olfactory measures. Genome-wide association studies have identified loci in taste and olfactory receptor genes associated with specific chemosensory traits as well as liking and intake of various foods, although the evidence remains concentrated on bitter taste and populations of European ancestry. These genetic variants have been used in Mendelian randomisation, a genetics-based approach that strengthens causal inference, to test whether sensory traits influence dietary behaviour. For precision nutrition, evidence for taste genotype-stratified interventions remains limited and mixed. Realising the promise of sensory nutrition will require scalable and standardised chemosensory phenotyping, Findable, Accessible, Interoperable, and Reusable (FAIR) data infrastructure, expanded research in diverse populations, and integration with broader biological and sociocultural determinants of dietary intake.

Genetics↗
PubMed2005

Genome-wide association studies for common diseases and complex traits.

Genetic factors strongly affect susceptibility to common diseases and also influence disease-related quantitative traits. Identifying the relevant genes has been difficult, in part because each causal gene only makes a small contribution to overall heritability. Genetic association studies offer a potentially powerful approach for mapping causal genes with modest effects, but are limited because only a small number of genes can be studied at a time. Genome-wide association studies will soon become possible, and could open new frontiers in our understanding and treatment of disease. However, the execution and analysis of such studies will require great care.

Animals↗
PubMedDate not supplied

GeneClinics: a hybrid text/data electronic publishing model using XML applied to clinical genetic testing.

GeneClinics is an online genetic information resource consisting of descriptions of specific inherited disorders ("disease profiles") as well as information on the role of genetic testing in the diagnosis, management, and genetic counseling of patients with these inherited conditions. GeneClinics is intended to promote the use of genetic services in medical care and personal decision making by providing health care practitioners and patients with information on genetic testing for specific inherited disorders. GeneClinics is implemented as an object-oriented database containing a combination of data and semistructured text that is rendered as HTML for publishing a given "disease profile" on the Web. Content is acquired from authors via templates, converted to an XML document reflecting the underlying database schema (with tagging of embedded data), and then loaded into the database and subjected to peer review. The initial implementation of a production system and the first phase of population of the GeneClinics database content are complete. Further expansion of the content to cover more disease, significant scaling up of rate of content creation, and evaluation redesign are under way. The ultimate goal is to have an entry in GeneClinics for each entry in the GeneTests directory of medical genetics laboratories-that is, for each disease for which clinical genetic testing is available.

Causality↗
PubMed2006

Development of a molecular genetic linkage map for Colletotrichum lindemuthianum and segregation analysis of two avirulence genes.

A framework genetic map was developed for the fungal pathogen Colletotrichum lindemuthianum, the causal agent of anthracnose of common bean (Phaseolus vulgaris L.). This is the first genetic map for any species within the family Melanconiaceae and the genus Colletotrichum and provides the first estimate of genome length for C. lindemuthianum. The map was generated using 106 haploid F1 progeny derived from crossing two Mexican C. lindemuthianum isolates differing in two avirulence genes (AvrclMex and AvrclTO). The map comprises 165 AFLP markers covering 1,897 cM with an average spacing of 11.49 cM. The markers are distributed over 19 major linkage groups containing between 5 and 25 markers each and the genome length was estimated to be approximately 3,241 cM. The avirulence genes AvrclMex and AvrclTO segregate in a 1:1 ratio supporting the gene for gene hypothesis for the incompatible reaction between C. lindemuthianum and P. vulgaris, but could not be incorporated into the genetic map. This initial outline map forms the basis for the development of a more detailed C. lindemuthianum linkage map, which would include other types of molecular markers and allow the location of genes previously isolated and characterized in this species.

Colletotrichum↗
PubMed1992

The genetics of malignant melanomas.

A review of the hereditary aspects of the malignant melanomas showed causal heterogeneity and similar pathogenesis based on the dysregulation of the paracrine/autocrine growth mechanisms. The genetically different malignant melanomas have a range of recurrence risks from 1% for the nonfamilial, solitary, malignant melanoma to a risk exceeding 70% for the syndromic melanomas of neurocutaneous melanosis and the nine types of xeroderma pigmentosum. A recurrence risk of 6% is relevant to the members of dysplastic nevus syndrome families without malignant melanomas and the risk increases in excess of 50% for the individuals of families with dysplastic nevi and more than one malignant melanoma.

Cytogenetics↗
PubMed2003

The genetic loci of open-angle glaucoma.

As Posner stated in 1949, the bottom line "to the patient and to his family is..., whether his disease will follow a mild course or will lead to blindness". The final goal of genetic research is the identification of the causal genes in the patient, to aid the ophthalmologist in predicting the outcome, in determining diligent treatment is required, and ultimately, in providing the tools for preventing blindness.

Chromosome Mapping↗
PubMed2003

Using mice to decipher the molecular genetics of brain tumors.

The past decade has dramatically increased our knowledge of genetic and molecular alterations in human central nervous system tumors. Important as these alterations are for the molecular classification of tumors, their actual roles in tumorigenesis and tumor progression have long remained obscure. Lately, several mouse brain tumor models have been developed that use different gene modification strategies to replicate mutations seen in the human counterpart. These genetic models will allow discrimination between mutations that are causally related to tumor formation and mutations that are a result of tumor progression. These models also provide histologically and genetically accurate models for preclinical testing and will perhaps help us identify novel targets for therapies aimed at the mechanistic cause of the disease. We present here a review of current models, with a focus on gliomas and medulloblastomas.

Animals↗
PubMedDate not supplied

Molecular epidemiology: a new perspective for the study of toxic exposures in man. A consideration of the influence of genetic susceptibility factors on risk in different lung cancer histologies.

This data in the aggregate suggests that the 3 best studied genetic susceptibility factors (CYP2D6 extensive metabolizers, GST mu null phenotype, and CYP1A1 "mutant" alleles in Asians only) constitute greater risk factors for the more smoking related histologies of lung cancer, but not for adenocarcinoma. The epidemiologic evidence for a these genetic susceptibility factors in tobacco-related cancer is suggestive but not determinant. A consensus estimate of relative risk for extensive metabolizers of debrisoquine is around 2. Variability in study results depend on a number of factors which include: assay misclassification, non-correspondence of phenotype/genotype in certain subjects, disease heterogeneity, exposure variation, ethnic and racial variation. Future studies should emphasize: a high quality approach to data gathering, careful attention to epidemiologic design, and the use of intermediate markers where feasible. Investigators should consider the use of multiple genetic markers since PCR approaches can make this an efficient approach. A meta-analysis may serve to illuminate points of heterogeneity between studies. New discoveries should provide opportunities to explore for analogous associations in other malignancies. It may be speculated that the "specificity" of the association observed for each of the genetic factors tends to support the general causal nature of the hypothesis. The fact that each shares the histologic preference at least suggests that a common mechanism may be operative. The observation that the tobacco-cancer association, though clearly present, is weaker for adenocarcinoma than for the other lung cancer histologies, suggests that the underlying mechanism involves some interaction of the genetic trait with exposure to tobacco smoking, and suggests further attention to this factor to elucidate differences in risk estimates for genetic susceptibility factors among different studies.

Disease Susceptibility↗