PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Multifactorial Inheritance”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1999

Significant evidence for linkage of a simulated trait to D1G024--a conclusion reached using multiallelic transmission/disequilibrium tests.

We applied three versions of the transmission/disequilibrium test (TDT) for detecting linkage in nuclear families using the a priori information of possibly present association. For our analyses we employed all marker data for a simulated trait. Results for replicate 11 showed significant linkage to D1G024 using the multiallelic Tmhet statistic and the extended TDT. The TDT for the most frequent parental allele which had been applied successfully in previous studies failed to detect linkage. This result may have happened because the data did not arise from a realistic simulation of the evolution of a real population, where mutations might be expected to occur against a specific haplotype. Simulation studies are required to elucidate the applicability of the TDT for the most frequent parental allele in realistic situations. Furthermore, guidelines have to be developed for how to pool categories in large, sparse contingency tables to obtain larger cell frequencies and lower degrees of freedom.

Alleles↗
PubMed2005

Genotyping errors, pedigree errors, and missing data.

Our group studied the effects of genotyping errors, pedigree errors, and missing data on a wide range of techniques, with a focus on the role of single-nucleotide polymorphisms (SNPs). Half of our group used simulated data, and half of our group used data from the Collaborative Study on the Genetics of Alcoholism (COGA). The simulated data had no missing genotypes and no genotyping errors, so our group, as a whole, removed data and introduced artificial errors to study the robustness of various techniques. Our teams showed that genotyping errors are less detectable and may have a greater impact on SNPs than on microsatellites, but recently developed methods that account for genotyping errors help reduce false positives, and the assumptions of these methods appear to be supported by observations from repeated genotyping. The ability to detect linkage disequilibrium (LD) was also substantially reduced by missing data; this in turn could affect tagging SNPs chosen to generate haplotypes. In the COGA sample, genotyping measurements were repeated in three ways. First, full-genome screens were performed on three sets of markers: 328 microsatellites, 11,560 SNPs from the Affymetrix GeneChip Mapping 10 K Array marker set, and 4,720 SNPs from the Illumina Linkage III panel. Second, the entire Affymetrix marker set was typed on the same 184 individuals by two different laboratories. Finally, the Affymetrix and Illumina marker panels had 94 SNPs in common. Our teams showed that both SNPs and microsatellites can be readily used to identify pedigree errors, and that SNPs have fewer genotyping errors and a low inconsistency rate. However, a fairly high rate of no-calls, especially for the Affymetrix platform, suggests that the inconsistency rate may be higher than observed.

Alcoholism↗
PubMed2006

The effect of reduction in cross-validation intervals on the performance of multifactor dimensionality reduction.

Multifactor Dimensionality Reduction (MDR) was developed to detect genetic polymorphisms that present an increased risk of disease. Cross-validation (CV) is an important part of the MDR algorithm, as it prevents over-fitting and allows the predictive ability of a model to be evaluated. CV is a computationally intensive step in the MDR algorithm. Traditionally, MDR has been implemented using 10-fold CV. In order to reduce computation time and therefore allow MDR analysis to be applied to larger datasets, we evaluated the possibility of eliminating or reducing the number of CV intervals used for analysis. We found that eliminating CV made final model selection impossible, but that reducing the number of CV intervals from ten to five caused no loss of power, thereby reducing the computation time of the algorithm by half. The validity of this reduction was confirmed with data from an Alzheimer's disease (AD) study.

Alzheimer Disease↗
PubMed2007

MCMC-based linkage analysis for complex traits on general pedigrees: multipoint analysis with a two-locus model and a polygenic component.

We describe a new program lm_twoqtl, part of the MORGAN package, for parametric linkage analysis with a quantitative trait locus (QTL) model having one or two QTLs and a polygenic component, which models additional familial correlation from other unlinked QTLs. The program has no restriction on number of markers or complexity of pedigrees, facilitating use of more complex models with general pedigrees. This is the first available program that can handle a model with both two QTLs and a polygenic component. Competing programs use only simpler models: one QTL, one QTL plus a polygenic component, or variance components (VC). Use of simple models when they are incorrect, as for complex traits that are influenced by multiple genes, can bias estimates of QTL location or reduce power to detect linkage. We compute the likelihood with Markov Chain Monte Carlo (MCMC) realization of segregation indicators at the hypothesized QTL locations conditional on marker data, summation over phased multilocus genotypes of founders, and peeling of the polygenic component. Simulated examples, with various sized pedigrees, show that two-QTL analysis correctly identifies the location of both QTLs, even when they are closely linked, whereas other analyses, including the VC approach, fail to identify the location of QTLs with modest contribution. Our examples illustrate the advantage of parametric linkage analysis with two QTLs, which provides higher power for linkage detection and better localization than use of simpler models.

Chromosome Mapping↗
PubMed2001

Heritability of hippocampal size in elderly twin men: equivalent influence from genes and environment.

Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories.

Aged↗
PubMed2001

Statistical multilocus methods for disequilibrium analysis in complex traits.

Hundreds of thousands of SNP markers are being generated with the purpose of carrying out case-control association studies for complex traits, which are thought to be due to multiple underlying susceptibility genes. The number of markers is typically much larger than the number of observations so that joint analysis of marker genotypes and their interactions is not feasible. We discuss a two-stage approach to first select a small subset of markers and then model the effects of the selected markers on disease. Examples of two procedures for marker selection are given with subsequent modeling of main and interaction effects. The approaches are applied to a data set with 89 SNPs in lieu of a genome screen with many more markers.

Alleles↗
PubMed2006

Gender-specific polygenic control of ethylnitrosourea-induced oncogenesis in the rat peripheral nervous system.

The inbred BD rat strains constitute a model system for analysis of the genetic basis of susceptibility or resistance to the development of neural tumors, as they exhibit distinct strain-specific differences regarding the sensitivity to tumor induction by the alkylating carcinogen N-ethyl-N-nitrosourea (EtNU). Among the different BD strains, BDIX and BDIV rats, respectively, are either highly susceptible or entirely resistant to the development of EtNU-induced malignant schwannomas of the peripheral nervous system (PNS), predominantly of the trigeminal nerves. We have previously mapped one locus associated with susceptibility/resistance to schwannoma induction to the telomeric third of chromosome 10 (Mss1) in segregating (BDIX x BDIV) crosses. We report on the genetic mapping of 6 further loci controlling tumor incidence or survival time on chromosomes 1 (Mss2), 3 (Mss3), 6 (Mss4), 13 (Mss5) and 15 (Mss6) as well as on chromosome 10 (Mss7) close to the centromere. Interestingly, most of these loci mediate gender-specific effects of variable strength ranging from minor influences on tumor development to complete tumor resistance. The gender specificity is reflected by the fact that male (BDIX x BDIV) F2 rats exhibit a 2-fold higher incidence of EtNU-induced schwannomas than females as well as a shorter survival time. A number of human nervous system tumors too arise with a marked gender bias. Genes mediating gender-specific predisposition of developing malignant schwannomas in the rat may be relevant for the human individual risk of developing nervous system tumors.

Alkylating Agents↗
PubMed1995

Frequency and characteristics of familial aggregation of Paget's disease of bone.

The cause of Paget's disease of bone (PDB) is unknown. In an attempt to ascertain the proportion of familial cases and evaluate the influence of genetic factors on the occurrence of the disease, a study was undertaken based on 35 PDB patients from our Unit. Their families were investigated, with the participation of a total of 128 first-degree relatives. Fourteen (40%) of these 35 index cases had at least one other first-degree relative affected with PDB and were defined as "familial." The remaining 21 (60%) were considered "sporadic." The frequency of males in the familial cases (79%) was significantly higher than among the sporadics (29%; p < or = 0.01). Mean age at diagnosis (63.1 +/- 12.6 vs. 71.3 +/- 8.7; p < or = 0.02), proportion of polyostotic cases (85.7% vs. 52.4%, p < or = 0.05), and mean number of involved bones per patient (4.36 +/- 2.50 vs. 2.33 +/- 1.93, p < or = 0.01) differ significantly in the familial and sporadic groups. The disease appears to be transmitted via both paternal and maternal sides, and pedigree analysis suggested an autosomal dominant inheritance or multifactorial mechanism. Apart from green-and-blue eye color, which was clearly associated with familial grouping (OR 6.25, 95% CI 1.15-37.16, p < or = 0.01), crude analysis on several genetically based traits and environmental variables revealed no other significant differences between the groups. The adjusted odds ratio estimated for green-and-blue eye color was 2.92 (95% CI 0.38-22.74).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2025

Protective Effects of Genetic Proxies of Cognitive Reserve in Parkinson's Disease: A Longitudinal Multi-Cohort Study.

BACKGROUND: Resilience factors are crucial in the progression of neurodegenerative diseases. However, it remains unclear whether a genetic predisposition to cognitive reserve influences clinical heterogeneity in the prognosis of Parkinson's disease (PD). OBJECTIVES: The aim is to evaluate the utility of polygenic scores (PGSs) for cognitive reserve proxies, including intelligence (INT), educational attainment (EA), and occupational attainment (OA), in predicting the clinical progression of PD. METHODS: Genetic and clinical data for progression of PD (progression to Hoehn and Yahr stage &#x2265;3, progression to a Montreal Cognitive Assessment score&#x2009;&#x2264;24, and occurrence of psychosis) were obtained from the Accelerating Medicine Partnership Parkinson's Disease database. We conducted multivariate Cox regression analysis, adjusting for relevant covariates, including years of education, variants in APOE, GBA1, LRRK2, and other cognitive reserve-related PGSs. RESULTS: All cognitive reserve-related PGSs significantly reduced the risk of cognitive decline, and EA-PGS (hazard ratio [HR], 0.550; 95% confidence interval [CI], 0.447-0.676; P&#x2009;<&#x2009;0.001) remained significant after controlling for INT-PGS and OA-PGS. EA-PGS (HR, 0.805; 95% CI, 0.672-0.964; P&#x2009;=&#x2009;0.019) was significantly associated with better motor prognosis after controlling for other PGSs. OA-PGS was linked to a decreased risk of developing psychosis in PD and remained significant after adjusting for others (HR, 0.784; 95% CI, 0.631-0.975; P&#x2009;=&#x2009;0.029). CONCLUSIONS: Genetic proxies of cognitive reserve are associated with a reduced risk of cognitive decline, motor progression, and development of psychosis in PD. These findings may enhance our understanding of individual differences in resilience in progression of PD. &#xa9; 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Humans↗
PubMed2003

Genetic basis of resistance and studies on cross-resistance in a population of diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

The genetic basis of abamectin resistance was studied in a strain of the diamondback moth, Plutella xylostella (L), following laboratory selection of a field population collected at Xuanhua, Hebei Province, China. Data from the testing of F1 progeny from reciprocal crosses between abamectin-resistant and abamectin-susceptible strains indicated that resistance might be autosomal and incompletely recessive with a degree of dominance of -0.13. Chi-squared analyses from the response of a backcross of crossed F1 progeny and the resistant strain and F2 progeny were highly significant, suggesting that the resistance was probably controlled by more than one gene. The results of cross-resistance studies showed that there was little cross-resistance between abamectin and four pyrethroid insecticides (deltamethrin, beta-cypermethrin, fenvalerate and bifenthrin) and no cross-resistance between abamectin and the acylureas chlorfluazuron or flufenoxuron.

Animals↗
PubMed2000

Multiplex PCR for detection of trait and virulence factors in enterohemorrhagic Escherichia coli serotypes.

A multiplex PCR assay was developed which allowed the simultaneous detection of five trait genes or virulence markers in enterohemorrhagic Escherichia coli (EHEC) serotypes. A primer pair, designed to detect a single base-pair mutation in the uidA gene, is specific only for the prototypic EHEC of O157:H7 serotype and its toxigenic, non-motile variants. In a similar way, primers to the eaeA gene of the gamma-intimin derivative specifically detects strains in the EHEC 1 clonal group, which consists mostly of O157:H7 and some O55:H7 serotypes. The other three primer pairs, specific for stx1, stx2 and both variants of ehxA genes, will detect the presence of these virulence genes in all EHEC serotypes. Analysis of 34 strains, including various serotypes of EHEC, Shiga toxin-producing E. coli and enteropathogenic E. coli, confirmed that the multiplex PCR assay detected the presence of these genes in a manner consistent with the known genotype of each respective strains.

Bacterial Proteins↗
PubMed2003

Novel approaches to identify low-penetrance cancer susceptibility genes using mouse models.

Studies of cancer predisposition have largely concentrated on the role of high-penetrance susceptibility genes. Less than 10% of the total human tumor burden, however, is accounted for by mutations in these genes. More genetic variation in cancer risk is likely to be due to commoner but lower penetrance alleles. In man, such modifier genes will be difficult to find since they do not segregate as single Mendelian traits. The mouse offers a powerful system for studying polygenic traits such as cancer and has been widely used for this purpose. Novel approaches that might accelerate the identification of these low-penetrance cancer susceptibility genes by using mouse models will be discussed.

Alleles↗
PubMed1983

Family study of congenital limb reduction abnormalities in Hungary 1975-1977.

A family study of 274 index patients with limb reduction malformations born in Hungary from 1975 to 1977 is reported. The majority of 789 first-degree relatives were personally examined. Information was collected on 1094 uncles and aunts and on 1095 cousins, and those affected by limb malformations were examined. Among 789 first-degree relatives six were affected by a similar malformation (radial, ulnar and central ray defects) and 1 by a malformation of a different type; no secondary cases of the same type were found among the relatives of patients with terminal transverse and amniogenic malformations, and with limb malformations which were part of syndromes or unclassifiable associations with other malformations. While a few rare types of limb defects are due to dominant genes, the aetiology of most cases is obscure. There is no evidence of sex-linked inheritance, of multifactorial causation or of environmental factors shared by relatives. These results are similar to those of an earlier study by Birch-Jensen.

Abnormalities, Multiple↗
PubMed2003

Accuracy of marker-assisted selection with auxiliary traits.

Genetic information on molecular markers is increasingly being used in plant and animal improvement programmes particularly as indirect means to improve a metric trait by selection either on an individual basis or on the basis of an index incorporating such information. This paper examines the utility of an index of selection that not only combines phenotypic and molecular information on the trait under improvement but also combines similar information on one or more auxiliary traits. The accuracy of such a selection procedure has been theoretically studied for sufficiently large populations so that the effects of detected quantitative trait loci can be perfectly estimated. The theory is illustrated numerically by considering one auxiliary trait. It is shown that the use of an auxiliary trait improves the selection accuracy; and, hence, the relative efficiency of index selection compared to individual selection which is based on the same intensity of selection. This is particularly so for higher magnitudes of residual genetic correlation and environmental correlation having opposite signs, lower values of the proportion of genetic variation in the main trait associated with the markers, negligible proportion of genetic variation in the auxiliary trait associated with the markers, and lower values of the heritability of the main trait but higher values of the heritability of the auxiliary trait.

Animals↗
PubMed2002

The power and statistical behaviour of allele-sharing statistics when applied to models with two disease loci.

We have evaluated the power for detecting a common trait determined by two loci, using seven statistics, of which five are implemented in the computer program SimWalk2, and two are implemented in GENEHUNTER. Unlike most previous reports which involve evaluations of the power of allele-sharing statistics for a single disease locus, we have used a simulated data set of general pedigrees in which a two-locus disease is segregating and evaluated several nonparametric linkage statistics implemented in the two programs. We found that the power for detecting linkage using the S(all) statistic in GENEHUNTER (GH, version 2.1), implemented as statistic E in SimWalk2 (version 2.82), is different in the two. The P values associated with statistic E output by SimWalk2 are consistently more conservative than those from GENEHUNTER except when the underlying model includes heterogeneity at a level of 50% where the P values output are very comparable. On the other hand, when the thresholds are determined empirically under the null hypothesis, S(all) in GENEHUNTER and statistic E have similar power.

Alleles↗
PubMed1999

The 677T genotype of the common MTHFR thermolabile variant and fasting homocysteine in childhood venous thrombosis.

Controlled data on the association of MTHFR genotypes, hyperhomocysteinaemia and their interaction with factor V G1691A with childhood thrombosis are not yet available. Therefore we conducted a case-control study comparing 141 childhood patients with venous thrombosis with 345 healthy controls. The MTHFR C677T genotypes, FV G1691A and prothrombin G20210A were evaluated; in addition, fasting homocysteine concentrations were measured in a subgroup of 60 children and 80 healthy controls. 10.4% of the healthy control population showed the MTHFR TT genotype, 34.2% the CT genotype and 55.4% the CC variant. MTHFR genotypes account for fasting homocysteine concentrations in healthy controls (CC: 5.5 micromol/l (4-7.2); CT: 7 micromol/l (3.9-9.8); TT: 12.1 micromol/l (7.7-13.3)) with an upper age-specific 95th percentile of 8.3 micromol/l. The following frequencies (patients versus controls), odds ratios (OR) and 95% confidence intervals (CI) were found for single defects: MTHFR 677TT genotype (10.6% vs. 10.4%; OR/CI: 1.02/0.54-1.93; P = 0.99) and CT genotype (43.8% vs. 34.2%; OR/CI: 2.12/1.42-3.16; P = 0.0000). A combination of FV G1691A mutation and MTHFR 677CT genotype was found in 9.9% of patients and in 2.9% of the controls (OR/CI: 3.8/1.64-8.75; P = 0.027). Fasting homocysteine median (range) concentrations in the patient group were significantly higher than in the controls (7 micromol/l (3-23) vs. 5.5 micromol/l (3-8.4): P = 0.0004), and homocysteine concentrations >8.3 micromol/l were found in 40% of patients vs. 2.5% of the controls (OR/CI: 22/2.64-183; P = 0.0003). Conclusion Data of this childhood case-control study suggest that mildly elevated fasting homocysteine concentrations >8.3 micromol/l and the CT genotype of the MTHFR C677T variant are significant risk factors for venous vascular occlusion in children.

Adolescent↗
PubMed2004

SLC22A4 and RUNX1: identification of RA susceptible genes.

Recently we reported that SLC22A4 and RUNX1 are associated with rheumatoid arthritis (RA). SLC22A4 is an organic cation transporter with unknown physiological function, and RUNX1 is a hematological transcriptional regulator that has been shown to be responsible for acute myelogenic leukemia. It is suggested that the association of RUNX1 with RA is due to its regulation of expression of SLC22A4. Because the physiological function of SLC22A4 is still unclear, further investigation is needed into how SLC22A4 affects RA susceptibility. Although the association of RUNX1 with RA was identified as a regulatory factor of SLC22A4, it is possible that RUNX1 is a key molecule in autoimmunity, as it has been reported to be associated with systemic lupus erythematosus and psoriasis, two other autoimmune diseases.

Animals↗