bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and environmental effects on blood pressure in a Norwegian sample
Authors: Tambs Kristian , Moum Torbjørn , Holmen Jostein , Eaves Lindon J. , Neale Michael C. , Lund‐Larsen Per G. , Naess Siri , Vogler G. P. 
Published: June 2005

AbstractSystolic (SBP) and diastolic (DBP) blood pressures were measured in a health screening of the adult population in Nord‐Trøndelag, Norway. Correlations were computed for 23,936 pairs of spouses, 43,586 pairs of parent and offspring, 19, 151 pairs of siblings, 1,251 pairs of grandparents‐grandchildren, 1,146 pairs of biological uncles/aunts‐nephews/nieces (avuncular), 801 non‐biological avuncular pairs, 169 pairs of same‐sex twins, and smaller groups of other types of relationships. Spouse correlations of 0.08 and 0.09 were approximately constant or slightly decreasing with marital duration. The correlation values for SBP and DBP were approximately 0.16 for parents‐offspring, 0.19 to 0.23 for same‐sex siblings with similar values for DZ twins, 0.19 and 0.16 for opposite‐sex siblings, 0.52 and 0.43 for MZ twins, and close to zero for most of the second‐order relationships. Genetic additive variance was estimated at 0.29 and genetic dominance variance at 0.18 with the best model for SBP. The corresponding estimates from the best models for DBP were 0.29 or lower and 0.22 or lower, the sum not exceeding 0.35. There was evidence of a moderate effect of environmental factors shared by same‐sex siblings and twins (for DBP), but no cultural transmission, and whether or not adult relatives live together does not affect familial resemblance for BP. The data did not permit a very precise resolution of the relative magnitude of genetic dominance and sibling effects. The correlation structure did not show sex‐specific genetic effects. © 1992 Wiley‐Liss, Inc.
Two‐locus mitochondrial and nuclear gene models for mitochondrial disorders
Authors: Bu Xiangdong , Yang Hui‐ying , Shohat Mordechai , Rotter Jerome I. , Vogler G. P. 
Published: June 2005

AbstractStimulated by a large pedigree with a cochlear form of deafness, for which we considered a two‐locus mitochondrial and nuclear gene model, we have extended the classic methods of segregation analysis to these classes of two‐locus disorders. Based on the unique maternal transmission pattern of the mitochondria, we demonstrate that utilization of the maternal line pedigree allows us to simplify the various two‐locus mitochondrial models to ‘one nuclear locus’ models. Classifying the nuclear families into different independent groups by the mother's phenotypes allows us to estimate the nuclear gene frequency in one group and to use this estimate as the expected value to test the fitness of the model on the other group. In addition, if we restrict the analysis to specific subsets of the mating type(s), we can also test the model on specific groups of nuclear families without estimating the gene frequency. Goodness‐of‐fit tests can be performed on pooled sibship data as well as individual sibship data. These methods of analysis should assume increasing importance as more disorders with features of mitochondrial inheritance are identified. © 1992 Wiley‐Liss, Inc.
Sensitivity of transmission probabilities to paternity exclusion in segregation analysis
Authors: Bonaïti‐pellié Catherine , Poisson Nicole , Bechtel Yvette , Bechtel Pierre , Vogler G. P. 
Published: June 2005

AbstractPaternity exclusions are known to be common in Western countries and are yet neglected in segregation analysis because it is almost impossible to check it systematically on a large family sample. We had the opportunity of observing the sensitivity of segregation analysis parameters to a paternity exclusion in analyzing 34 families for a simple Mendelian trait, the acetylator phenotype. We found that only one family, with proven paternity exclusion, was responsible for a strong rejection of Mendelian transmission probabilities (P≪0.001). © 1992 Wiley‐Liss, Inc.
Extended pedigree patterned covariance matrix mixed models for quantitative phenotype analysis
Authors: Schork Nicholas J. , Vogler G. P. 
Published: June 2005

AbstractOvert computational constraints in the formation of mixed models for the analysis of large extended‐pedigree quantitative trait data which allow one to reliably characterize and partition sources of variation resulting from a variety sources have proven difficult to overcome. The present paper suggests that by combining a restricted patterned covariance matrix approach to modeling and partitioning the variation arising from polygenic and environmental forces with an Elston–Stewart like algorithmic approach to modeling variation resulting from a single genetic locus with large phenotypic effects one can produce a model that is at once intuitively appealing, efficient computationally, and reliable numerically. Extensions and variations of this approach are also discussed, as are some simulation and timing studies carried out in an effort to validate the accuracy and computational efficiency of the proposed methodology. © 1992 Wiley‐Liss, Inc.
Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world
Authors: Gerdes Lars Ulrik , Klausen Ib Christian , Sihm Inger , Faergeman Ole , Vogler G. P. 
Published: June 2005

AbstractApolipoprotein E (apoE) phenotypes were determined in a random sample of 466 Danish men born in 1948. The frequencies of the common alleles of the apoE gene were (with 95% confidence intervals) ϵ2 = 0.085 (0.068–0.105), ϵ3 = 0.741 (0.712–0.769), and ϵ4 = 0.174 (0.150–0.200). These frequencies were compared to findings in 45 other study populations around the world (n > 100). The Danish population was found to cluster with populations from Iceland, Norway, Iceland, Scotland, the Netherlands, Germany, France (Paris), and Caucasian populations in Canada and the USA. The compiled data further show that dissimilarities in apoE allele frequencies among Caucasian populations are comparable to dissimilarities between some Caucasian and Asian populations. Notably, the frequency of ϵ4 appears to be higher in northern regions of Europe (the Nordic countries, Scotland, Germany, and the Netherlands) than in southern regions (Switzerland, Tyrol, France [Nancy], Italy, and Spain). © 1992 Wiley‐Liss, Inc.
Genetic variation in two bone‐related proteins: Is there an association with bone mineral density or skeletal size in postmenopausal women?
Authors: Eichner J. E. , Cauley J. A. , Ferrell R. E. , Cummings S. R. , Kuller L. H. , Vogler G. P. 
Published: June 2005

AbstractIn an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non‐Black women (age 65–90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone‐related proteins, group specific component (Gc), also known as vitamin D‐binding protein, and α2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P<.02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding. © 1992 Wiley‐Liss, Inc.
Influence of polymorphisms for apolipoprotein B (ins/del,Xbal,EcoRI)and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population
Authors: Gajra B. , Candlish J. K. , Saha N. , Heng C. K. , Soemantri A. G. , Tay J. S. H. 
Published: June 2005

AbstractA total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del,XbaI, andEcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09;X+, 0.1; andR−, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy‐Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between theins/delandXbaI site polymorphisms of apo B (χ42= 25.3;P< 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except forXabI, which appeared to be associated with serum TG (as the log transform:R2= 8.3;F= 4.8;P< 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low‐density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F= 5.4;P< 0.01). © 1994 Wiley‐Liss, Inc.
Survival models for developmental genetic data: Age of onset of puberty and antisocial behavior in twins
Authors: Pickles Andrew , Crouchley Robert , Simonoff Emily , Eaves Lindon , Meyer Joanne , Rutter Michael , Hewitt John , Silberg Judy 
Published: June 2005

AbstractThe use of survival analysis for developmental genetic data is discussed. The main requirements for models based on the decomposition of frailty distributions into shared and unshared components are outlined for the simple case of twins. Extending the earlier work of Clayton, Oakes, and Hougaard, among others, three forms of hazard model are presented, all of which can be applied to pedigree data with flexible baseline hazards without the use of numerical integration. The first two models use an additive decomposition of frailty, with either gamma or positive stable law distributed (PSL) components. The third model previously described by Hougaard involves a multiplicative PSL decomposition. The models are applied to data on the onset of puberty in male twins and illustrate the importance of correct specification of the baseline hazard for correct inference about genetic effects. The difficulty of assessing model specification using information only on the margins is also noted. Overall, the new model with additive PSL components appeared to fit these data best. A second application illustrates the use of a time‐varying covariate in examining the impact of puberty on the onset of conduct disorder symptomotology. © 1994 Wiley‐Liss, Inc.
Robust genetic linkage analysis based on a score test of homogeneity: The weighted pairwise correlation statistic
Authors: Commenges D. 
Published: June 2005

AbstractIn testing genetic linkage using large or complex pedigrees, robust methods may be preferred to the Lod‐score method. The affected‐pedigree‐member method is robust but does not use the information available in nonaffected subjects, which results in a loss of power. We propose a new test of genetic linkage based on a score test of homogeneity derived from a random effect model. The statistic is simple and uses only pairs of subjects. In contrast with the affected‐pedigree‐method, it uses all the available pairs and does not depend on the marker alleles frequencies. A rank version of this weighted pairwise correlation statistic is proposed, its exact first and second moment derived. We show that for age‐dependent diseases, it provides a simple nonparametric test. © 1994 Wiley‐Liss, Inc.
Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study
Authors: Talmud Philippa J. , Ye Shu , Humphries Steve E. ,   On Behalf of The Ears Group
Published: June 2005

AbstractThe effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (−75 bp) with plasma apo AI and high‐density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age‐ and sex‐matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non‐smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.
Commingling analysis of memory performance in elderly men
Authors: Palmer Christina G. S. , Wolkenstein Bonnie H. , La Rue Asenath , Swan Gary E. , Smalley Susan L. 
Published: June 2005

AbstractSmalley et al. [(1992) Genet Epidemiol 9:333–345] found evidence of a mixture of two distributions in memory performance among offspring of patients with dementia of the Alzheimer type (DAT), suggesting that these groups reflect genotypic subgroups of carriers and non‐carriers of a putative DAT gene. One prediction of this hypothesis is that, in the general population, two distributions of memory performance are present, with a smaller proportion of subjects in the low‐scoring cluster than that found among the offspring sample, but similar to the prevalence of DAT in the elderly community‐at‐large. Memory performance was investigated in a large sample of normal elderly males (N = 1,149; mean age = 71.4 ± 4.7 years) to test this hypothesis. Commingling analyses of performance on the Benton visual retention test demonstrated significant negative skewness in the distribution of memory performance, requiring a transformation to fit a single normal distribution. In the absence of a transformation, two distributions fit better than one, with 6% of subjects falling into a “low”‐scoring cluster. These findings are consistent with the hypothesis that memory performance may represent a premorbid or morbid difference in those who go on to develop, or currently have, DAT, possibly allowing identification of at‐risk carriers of a putative single major gene for DAT. © 1994 Wiley‐Liss, Inc.
Feasibility of half‐sibling designs for detecting a genetic component to a disease
Authors: Tierney Camlin , Merikangas Kathleen R. , Risch Neil 
Published: June 2005

AbstractIn genetic epidemiology, adoption and twin study designs are the most commonly used designs to identify genetic and common environmental components underlying familial aggregation. Other fixed family set designs such as a half‐sibling design can also be applied to test the same hypotheses. The feasibility of half‐sibling designs for detecting a genetic (single‐locus or multifactorial) source of familial aggregation of a disease is studied and is compared to both adoption and twin study designs. Results are presented for two types of design where the sampling units are relative pairs reared apart (I) or reared together (II). Although they generally require more observations to achieve the same power, designs involving half‐siblings may be more feasible in situations where there is greater availability of these relatives. © 1994 Wiley‐Liss, Inc.
Interaction between genetic and environmental risk factors for Alzheimer's disease: A reanalysis of case‐control studies
Authors: Van Duijn C. M. , Clayton D. G. , Chandra V. , Fratiglioni L. , Graves A. B. , Heyman A. , Jorm A. F. , Kokmen E. , Kondo K. , Mortimer J. A. , Rocca W. A. , Shalat S. L. , Soininen H. , Hofman A. ,   EURODEM Risk Factors Research Group
Published: June 2005

AbstractTo study the interaction among genetic and environmental risk factors, a reanalysis of case‐control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising a total of 814 AD patients and 894 control subjects. When comparing those with a positive and negative family history of dementia, similar odds ratio were found for late maternal age [1.7; 95% confidence interval (0.6–4.8) vs. 2.0 (1.1–3.5)], head trauma [1.7 (0.7–4.2) vs. 1.9 (1.1–3.2)], and history of depression [2.0 (0.2–19.8) vs. 2.1 (0.8–1.7)]. This suggests a model in which these risk factors increase the risk for AD independent of family history of dementia. Among those with a positive family history of dementia, the odds ratios for family history of Down's syndrome [4.2 (0.9–20.0))] and of Parkinson's disease [3.3 (0.4–28.2)] tended to be higher than among those with a negative family history of dementia [2.6 (0.8–8.5) and 2.4 (0.8–7.0), respectively]. However, for both disorders the difference in odds ratio was not statistically significant. For history of cigarette smoking, there was no association to AD for those with no first degree relatives with dementia and an inverse relation with AD for those with a positive family history. Although in all analyses, family history of dementia remained significantly associated with AD in the absence of other factors, the odds ratio associated with family history of dementia tended to be lower for those with a positive smoking history, particularly for those with two or more affected relatives. These findings suggest that smoking may interact specifically with a genetically determined process. © 1994 Wiley‐Liss, Inc.
Complex segregation analysis of leprosy in Southern Vietnam
Authors: Abel Laurent , Lap Vu Dinh , Oberti Jean , Van Thuc Nguyen , Van Cua Van , Guilloud‐Bataille Michel , Schurr Erwin , Lagrange Philippe H. 
Published: June 2005

AbstractTo investigate the nature of the genetic component controlling susceptibility to leprosy and its subtypes, 402 nuclear families were ascertained through a leprosy patient followed at the Dermatology Hospital in Ho Chi Minh City, Vietnam; 285 families were of Vietnamese origin and 117 were of Chinese origin with a higher proportion of lepromatous forms among Chinese patients. Segregation analyses were conducted using the model developed by Abel and Bonney [(1990) Genet Epidemiol 7:391–407], which accounted for variable age of onset and time‐dependent covariates. Three phenotypes were considered: leprosy per se (all forms of leprosy together), nonlepromatous leprosy, and lepromatous leprosy. For each of this phenotype, analyses were performed on the whole sample and separately on the Vietnamese and the Chinese families. The results showed that a single Mendelian gene could not account for the familial distributions of leprosy per se and its two subtypes in the whole sample. However, these results were different according to the ethnic origin of the families. In the Vietnamese subsample, there was evidence for a codominant major gene with residual familial dependences for the leprosy per se phenotype, and borderline rejection of the Mendelian transmission hypothesis for the nonlepromatous phenotype. In Chinese families, strong rejection of Mendelian transmission was obtained in the analysis of leprosy per se, and no evidence for a familial component in the distribution of the nonlepromatous phenotype was observed. For the lepromatous phenotype, the discrimination between models was poor, and no definitive conclusion could be reached. Referring to immunological data, we suggest that these results could be explained by a heterogeneity in the definition of the lepromatous phenotype. It is likely that progress in the understanding of the genetic components involved in the expression of leprosy will come from a better definition of the phenotype under study, and immunological studies are ongoing in this population to investigate this hypothesis. © Wiley‐Liss, Inc.
Phenotypic assortative mating in segregation analysis
Authors: Hasstedt Sandra J. 
Published: June 2005

AbstractA model of phenotypic assortative mating was developed for application in segregation analysis. The model assumed a constant spouse correlation across the range of a quantitative trait or the liability to a discrete trait. Four traits were analyzed to evaluate: (1) the feasibility of applying likelihood analysis to pedigree data in order to distinguish between assortative mating and shared environmental effects as the source of spouse correlation; and (2) the impact on segregation analysis of the failure to account for either assortative mating or shared environmental effects, as appropriate. Height ratio (the ratio of sitting to standing height) and eye color comprised the traits for which the observed spouse correlation reflected assortative mating; serum cholesterol and peptic ulcers (with genotypes defined by the ABO blood group) comprised the traits for which the observed spouse correlation reflected shared environmental effects. For all four traits the test statistics agreed with the known cause of spouse correlation; however, significance was not attained for height ratio or serum cholesterol. The ability to distinguish between the causes of spouse correlation in pedigree data presumably depends on trait and sample characteristics which remain to be delineated. Despite significant spouse correlation, its omission from the segregation analysis model did not undermine the inference of major locus inheritance for any of the four traits. However, the lack of an impact for these traits does not preclude an impact for other traits of ignoring the appropriate spouse correlation in segregation analysis. © 1995 Wiley‐Liss, Inc.