bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pedigree analysis of blood pressure in subjects from rural Greece and relatives who migrated to Melbourne, Australia
Authors: Hopper John L. , Macaskill Greg T. , Powles John W. , Ktenas Dimitri , Chakravarti Aravinda 
Published: June 2005

AbstractDiastolic blood pressure readings taken in 1983–1984 on 1,474 Greek individuals (628 living on the island of Levkada, 846 relatives having migrated to Melbourne, Australia) from 204 two generational pedigrees were analysed. Blood pressure was regressed as a quadratic in age by sex and migrant status, and on temperature. Variance increased with age and was greater in migrant males. The covariance between relatives in different countries was significant. Variation was modeled by a multivariate normal model for pedigree analysis in terms of genetic effects, a common environment effect, and effects particular to an individual. The genetic component was 25.9 mm Hg2, independent of sex and migrant status. Importantly, the common environment component was not significant. The third component was greatest in migrant males. Spouse correlation was −0.09 (SE = 0.03). Exclusion of 86 individuals who reported currently receiving medication for elevated blood pressure stabilised the variance and decreased the genetic component. The data suggest that familial aggregation of diasatolic blood pressure is due to genetic factors which produce the same variation in males and females, living on Levkada or in Melbourne. Nongenetic factors explain the greater variation in blood pressure of migrant males living in Melbourne. © 1992 Wiley‐Liss, Inc.
Dietary intake and gene variation influence the response of plasma lipids to dietary intervention
Authors: Talmud Philippa J. , Boerwinkle Eric , Xu Chun‐fang , Tikkanen Matti J. , Pietinen Pirjo , Huttunen Jussi K. , Humphries Steve , Chakravarti Aravinda 
Published: June 2005

AbstractWe have examined whether variation at the apolipoprotein (apo) B, apo E, apo AII, and apo AI‐CIII‐AIV genes affected the relationship between dietary intake and serum lipid traits in individuals who had participated in dietary intervention from a basal high fat diet to a low fat diet followed by a return to their natural diet, the switchback. On both the basal and switchback diets where the variance of dietary intake was great, there was a significant correlation between P/S ratio and serum total, low‐density lipoprotein (LDL) cholesterol, and apo A1 levels. In addition dietary cholesterol (dchol) levels correlated significantly with serum apo A1 levels on the basal diet. Comparing the difference between basal and intervention (Δ1) and between switchback and intervention diets (Δ2), changes in dchol and P/S ratio correlated significantly with changes in serum total, high‐density lipo‐protein (HDL) and LDL cholesterol, and apo B levels. There was a significant correlation between monounsaturated fatty acid (MUFA) and apo A1 levels during both changes. Furthermore we have examined whether the relationship between variables was homogeneous among genotypes of candidate gene polymorphisms. A heterogeneous effect (P < 0.01) was seen among genotypes of the PvuII‐AIV restriction fragment length polymorphism (RFLP) on the correlation of serum LDL cholesterol levels and dietary MUFA during both dietary changes (Δ1 and Δ2). A heterogeneous effect among genotypes of the apo B XbaI RFLP on the correlation between dchol versus total and LDL cholesterol during the change Δ1, but not Δ2, was observed. Thus our results show that both dietary components and genetic variation affect the response of serum lipid, lipoprotein, and apolipoprotein levels to dietary change. © 1992 Wiley‐Liss, Inc.
Family study of α1‐antitrypsin deficiency: Effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits
Authors: Silverman Edwin K. , Province Michael A. , Campbell Edward J. , Pierce John A. , Rao D. C. , Boerwinkle Eric 
Published: June 2005

AbstractTo gain insight into the variable expression of lung disease in α1‐antitrypsin (α1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25–75), total serum α1AT, oxidized serum α1AT, and total serum immunoglobulin E (IgE) were measured in α1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total α1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25–75, and oxidized α1AT are moderately influenced by Pi type. The effect of genotype‐by‐environment interaction between Pi type and pack‐years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi × pack‐years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi × age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi × pack‐years interaction effect on FEV1 which Pi Z subjects ascertained for other reasons demonstrate. The effect of the Pi × pack‐years interaction on FEV1 was no longer significant on a transformed scale, (FEV12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi × packs‐years interaction effect on FEF25–75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype‐by‐environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals. © 1992 Wiley‐Liss, Inc.
Commingling analysis of memory performance in offspring of Alzheimer patients
Authors: Smalley Susan L. , Wolkenstein Bonnie H. , LaRue Asenath , Woodward J. Arthur , Jarvik Lissy F. , Matsuyama Steven S. , Chakravarti Aravinda 
Published: June 2005

AbstractDementia of the Alzheimer type (DAT) is a neurodegenerative disorder which afflicts approximately 3% of the population. Genetic influences are indicated from twin and family studies although genetic heterogeneity has been suggested from both pedigree analyses and linkage investigations. Autosomal dominant inheritance with age‐dependent penetrance has been suggested in at least some families with DAT. In the present investigation, we examine memory and nonmemory task performance in 106 asymptomatic offspring (mean age 40.6 years) of 54 DAT probands. Intraclass sibling correlations revealed little evidence of sibling similarity for performance on three memory tasks which have been reported to be relatively sensitive to the memory losses accompanying DAT. Subsequent investigations of the distributions of the cognitive task scores in the offspring revealed evidence for a commingling of two distributions for the three memory tasks but not for the nonmemory measures. These findings are consistent with a hypothesis that these distributions reflect genotypic subgroups, carriers, and noncarriers, of a presumed DAT gene. © 1992 Wiley‐Liss, Inc.
Two‐Locus models of disease
Authors: Neuman Rosalind J. , Rice John P. , Chakravarti Aravinda 
Published: June 2005

AbstractMost complex diseases have not been amenable to genetic analysis under the assumption of single locus or multifactorial models. Consequently, interest has turned to the consideration of the properties of oligogenic models. i.e., genetic models involving a small number of genes. Nine two‐locus models of disease, representing both epistatic and heterogeneous genetic models, are investigated: three models of heterogeneity and six models of epistatis. For each model we derive formulas for the recurrence risk to various classes of relatives in terms of penetrances and gene frequencies. We also develop formulas for the components of variance for the epistatic models in terms of the same genetic parameters. The range of penetrances and the associated gene frequencies that predict a predetermined value for the population prevalence and recurrence risk to the sibling of proband are calculated for various rates of the prevalence and risk to sibs. It is found that for many of these genetic models, there is a very limited range of penetrances that fit a particular set of assumed risks. Estimated population prevalence and risks to sibs and monozygotic twins for bipolar and schizophrenia illness are used to test for compatibility with expected values for recurrence risks under these models. © 1992 Wiley‐Liss, Inc.
Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits
Authors: Demenais Florence M. , Laing Amelia E. , Bonney George E. 
Published: June 2005

AbstractSegregation analysis of discrete traits can be conducted by the classical mixed model and the recently introduced regressive models. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affected persons have a liability exceeding a threshold. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype effects, the phenotypes of older relatives, and other covariates. A formulation of the regressive models, based on an underlying liability model, has been recently proposed. The regression coefficients on antecedents are expressed in terms of the relevant familial correlations and a one‐to‐one correspondence with the parameters of the mixed model can thus be established. Computer simulations are conducted to evaluate the fit of the two formulations of the regressive models to the mixed model on nuclear families. The two forms of the class D regressive model provide a good fit to a generated mixed model, in terms of both hypothesis testing and parameter estimation. The simpler class A regressive model, which assumes that the outcomes of children depend solely on the outcomes of parents, is not robust against a sib–sib correlation exceeding that specified by the model, emphasizing testing class A against class D. The studies reported here show that if the true state of nature is that described by the mixed model, then a regressive model will do just as well. Moreover, the regressive models, allowing for more patterns of family dependence, provide a flexible framework to understand gene–environment interactions in complex diseases. © 1992 Wiley‐Liss, Inc.
Genetic epidemiology of autosomal recessive spastic ataxia of Charlevoix‐Saguenay in northeastern Quebec
Authors: De Braekeleer M. , Giasson F. , Mathieu J. , Roy M. , Bouchard J. P. , Morgan K. 
Published: June 2005

AbstractAutosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) is a disorder that has an elevated frequency in Saguenay‐Lac‐St‐Jean (SLSJ) and Charlevoix, two geographically isolated regions in the past of northeastern Quebec. The incidence at birth and the carrier rate in SLSJ were estimated at 1/1,932 liveborn infants and 1/22 inhabitants, respectively, for the period 1941‐‐1985. The mean inbreeding coefficient was twice higher and the mean kinship coefficient 3 times higher among the ARSACS families than among control families. In the SLSJ region, the birth places of the ARSACS individuals and their parents did not show a clustered distribution. The genealogical reconstruction suggests that the high incidence of ARSACS in SLSJ and Charlevoix is likely to be the result of a founder effect. Because the disease is apparently unknown elsewhere in the world and a high proportion of French Canadians presently living in eastern Quebec have ancestors coming from Perche, a small region in France, it also suggests that a unique mutation accounts for most, if not all, of the ARSACS cases known in these regions. © 1993 Wiley‐Liss. Inc.
Role of genetic variation at the Apo AI‐CIII‐AIV gene cluster in determining plasma Apo AI levels in boys and girls
Authors: Xu Chun‐Fang , Angelico Francesco , Ben Maria Del , Humphries Steve 
Published: June 2005

AbstractWe have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (−75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8–11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II–CIII) and the apo CIII–AIV intergenic region (Pvu II–AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V−V+ of the G/A substitution and the PvuII–AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V−V−. In girls, however, there was evidence of significant interaction of effects between the PvuII–AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V+) of the PvuII–AIV RFLP. We conclude that genetic variation at the apo AI‐CIII‐AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII–CIII and PvuII–AIV polymorphisms. These effects are not modulated by diet but are modulated by other factors, possibly hormones, which are present in girls. © 1993 Wiley‐Liss. Inc.
Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia
Authors: Jarvik Gail Pairitz , Beaty Terri H. , Gallagher Paul R. , Coates Paul M. , Cortner Jean A. 
Published: June 2005

AbstractA sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 4l of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this “elevated apoB” allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL. © 1993 Wiley‐Liss, Inc.
AGFAP Method: Applicability under different ascertainment schemes and a parental contributions test
Authors: Thomson Glenys 
Published: June 2005

AbstractThe antigen/allele genotype frequencies among patients (AGFAP) method has been powerful in discriminating between modes of inheritance, and detecting heterogeneity effects, for a number of diseases associated with the HLA system. The method is not dependent on the high level of polymorphism seen in the HLA system, but does require a marker allele association with disease. With recent rapid advances in mapping of the human genome, the method is increasingly relevant in all disease studies. Extension of the AGFAP method to ascertainment schemes other than random sampling of patients is presented here. The method is shown to be robust for distinguishing between incompletely penetrant recessive vs. additive or dominant models if affected children are obtained from nuclear families selected on the basis of at least two affected members: two affected sibs, or an affected parent and affected child. The method can lead to false conclusions for data from families ascertained for at least one affected parent and two affected children. A new test, termed the parental contributions test, applicable in families selected for the presence of an affected parent, and one or more affected children, is presented. The test, based on the expected symmetry (recessive) vs. asymmetry (additive and dominant) of parental marker allele contributions to an affected offspring in these pedigrees, is powerful in distinguishing between these modes of inheritance when there is a marker allele association with disease. Sporadic cases of disease are shown to cause deviations from AGFAP expectations for the recessive model, but not for the additive model. These results will aid in study of the genetics, and hence molecular basis, of complex diseases. © 1993 Wiley‐Liss, Inc.
Sib‐pair linkage analyses of Alzheimer's disease
Authors: Bailey‐Wilson Joan E. , Bamba Vaneeta 
Published: June 2005

AbstractSib‐pair linkage analyses were used to search for linkage to a set of chromosome 19 and 21 marker loci in two sets of families with Alzheimer's disease. The advantage of this technique is that no assumption is made about the mode of inheritance of the disease. Some mild suggestions of linkage were found in early‐onset families for a chromosome 21 marker and in a set of late‐onset families for a chromosome 19 marker. © 1993 Wiley‐Liss, Inc.
Linkage detection by the Affected‐Pedigree‐Member method: What is really tested?
Authors: Babron Marie‐Claude , Martinez Maria , Bonaïti‐Pellié Catherine , Clerget‐Darpoux Françoise 
Published: June 2005

AbstractWe show that the null hypothesis in the Affected‐Pedigree‐Member (APM) method is composed of two sub‐hypotheses: no linkage and correct marker allele distribution. As a result, the APM method is not robust to misspecification of marker allele frequencies. © 1993 Wiley‐Liss, Inc.
Alzheimer's disease: A piscatorial trek
Authors: Van Eerdewegh Paul , Hampe Carol L. , Suarez Brian K. , Reich Theodore 
Published: June 2005

AbstractThe evidence for linkage between Alzheimer's disease and markers on both chromosomes 19 and 21 [Pericak‐Vance et al., 1991] by the affected‐pedigree‐member (APM) method [Weeks and Lange, 1988] cannot be replicated on any of the available GAW8 data sets when marker allele frequencies are estimated from the combined sample. The strong dependence of the APM method on accurate estimation of marker allele frequencies, and the effects of noninformative pairs and of genetic distance in informative pairs of relatives are illustrated. © 1993 Wiley‐Liss, Inc.
The impact of some parameters on linkage analysis of Alzheimer's disease
Authors: Xu J. F. , Taylor E. W. , Lung F. W. , Chung A. S. , Chase G. A. , Maestri N. E. , Meyers D. A. 
Published: June 2005

AbstractThe two‐point lod score linkage analysis of familial Alzheimer's disease is sensitive to the parameters of age‐dependent penetrance rate, phenocopy rate, heterogeneity, and marker gene frequency. If unsuitable parameters are used, it may lead to false negative evidence against linkage. However, it is clear that, in some cases, it may lead to false positive evidence of linkage. © 1993 Wiley‐Liss, Inc.
Is a single mutation at the same locus responsible for all affected cases in a large Alzheimer pedigree (FAD4)?
Authors: Martinez Maria , Campion Dominique , Babron Marie‐Claude , Clerget‐Darpoux Françoise 
Published: June 2005

AbstractAnalysis of marker segregation in the large Alzheimer pedigree, FAD4, leads to the conclusion, with a type I error of 5%, of linkage heterogeneity between two branches of the pedigree: the disease cosegregates with chromosome 21 markers flanking the APP area in one branch and not in the other one. Thus, we conclude that a single mutation in the chromosome 21 region surrounding APP cannot be responsible for all the affected cases in this pedigree. © 1993 Wiley‐Liss, Inc.
Combined segregation and linkage analysis of late‐onset Alzheimer's disease in Duke families using Gibbs sampling
Authors: Faucett Cheryl , Gauderman W. James , Thomas Duncan , Ziogas Al , Sobel Eugene 
Published: June 2005

AbstractWe illustrate the use of Gibbs sampling for combined segregation and linkage analysis using late‐onset families in the Duke Alzheimer's disease (AD) data set. The disease penetrance model is flexible, incorporating variable age of disease onset, sporadic cases, and unknown or uncertain ages of AD onset. Model parameters (including allele frequencies) and lod scores are estimated, and a correction for ascertainment is made. Little indication of linkage was observed for any chromosome 19 or 21 marker. However, there was strong evidence for the existence of an AD major gene under an autosomal dominant/sporadic model. © 1993 Wiley‐Liss, Inc.
Methods and applications of genetic analysis in the study of cardiovascular disease: A summary of contributions to GAW8
Authors: Wilson Alexander F. 
Published: June 2005

AbstractThe analyses of data provided for the cardiovascular disease section of Genetic Analysis Workshop 8 are briefly summarized. Methods using twin, segregation, and linkage analyses are used to determine, characterize, and localize genetic components involved in the etiology of cardiovascular disease and to explore the interaction of these components with known environmental risk factors. © 1993 Wiley‐Liss, Inc.
Lipid data from NHLBI veteran twins: Interpreting genetic analyses when model assumptions fail
Authors: Williams Christopher J. , Wijesiri U. W. L. 
Published: June 2005

AbstractAnalyses were performed on lipid data from the NHLBI Veteran Twin Study. The analyses focused on longitudinal multivariate models, describing how the genetic effects on lipids vary over time. Our pedigree‐based model selection approach allows simultaneous estimation of both covariance structure parameters and regression parameters. The analyses reveal strong correlations between additive genetic effects over time, implying that genetic effects on lipids are somewhat constant throughout the life span represented within this sample. Both univariate preliminary analyses and robust fitting applied to the longitudinal models indicate that several assumptions underlying the twin analyses are violated. Although variance component and correlation parameter estimates are not much changed by robust fitting analyses, questions remain about the behavior of parameter estimates in multivariate genetic models under departures from model assumptions. © 1993 Wiley‐Liss, Inc.