bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA class II typing using oligonucleotide probes
Authors: Robinson David M. , Holbeck Susan , Seyfried Christine , Byers Patricia , Palmer Jerry , Nepom Gerald T. 
Published: June 2005

AbstractA DQβ locus‐specific oligonucleotide probe is used to identify DQβ alleles present in six insulin‐dependent diabetes mellitus (IDDM) multiplex families. Results of genotyping using this technique agree with those from cDNA probes and are often clearer. Allele‐specific oligonucleotide probes for the DRβ locus are used to identify subtypes (Dw4 and Dw14) of the DR4 specificity in five IDDM multiplex families. This distinction cannot be made with available cDNA probes.
Genetic epidemiology of persistent islet cell antibodies among IDDM patients
Authors: Newman Beth , Selby Joseph , Lee Ming , King Mary‐Claire 
Published: June 2005

AbstractThe persistence of cytoplasmic islet cell antibodies (ICA) more than a year after diagnosis of insulin‐dependent diabetes mellitus (IDDM) was investigated in 43 families with at least two children with IDDM. The prevalence of persistent ICA among IDDM patients was 16%. Persistence of ICA appeared to be familial in that siblings with IDDM were significantly more concordant for the presence or for the absence of ICA than expected by chance (P = 0.04). Patients with persistent ICA were older on average at onset of IDDM than patients without persistent ICA after adjusting for duration of disease (P = 0.004). Persistence of ICA was not significantly associated with HLA DR type, immunoglobulin genotype, insulin allele class, sex, history of viral diseases, or prior vaccinations.
Description of amish study data set
Authors: Egeland Janice A. , Gerhard Daniela S. , Pauls David L. 
Published: June 2005

AbstractA brief description is given on the ascertainment methods and diagnostic procedures for bipolar affective disorder patients and their relatives in Amish pedigrees. Data on a sample of five bipolar families are provided, including conventional blood typings, serum protein and RFLP data.
Regressive logistic models for ordered and unordered polychotomous traits: Application to affective disorders
Authors: Bonney George E. , Dunston Georgia M. , Wilson Jerome 
Published: June 2005

AbstractRegressive models are extended to disease phenotypes with two or more affection classes through the use of polychotomous logistic regression. The classes of affection may be ordered (ranked as on a liability continuum), or unordered. Data on affective disorders are used for illustration.
Modelling sibship environment in the regressive logistic model for familial disease
Authors: Hopper John L. 
Published: June 2005

AbstractRecently analytical models for pedigree disease data have been developed that combine genetic and epidemiological modelling techniques. The regressive logistic model [Bonney, Biometrics 42:611–625; 1986] relies on decomposing the likelihood of a pedigree into the product of conditional probabilities, one for each individual, by imposing a (natural) order on pedigree members. In addition to modelling measured epidemiological variables, vertical transmission, transmission of unmeasured ousiotypes (a special case being genotypes), and some modelling of sibship dependencies have been proposed. In this paper the model is extended to include an unmeasured sibship environment factor using a log‐linear model for binary pedigree traits [Hopper et al., Genet Epidemiol 1:183–188; 1984], which breaks the pedigree into conditionally independent groups. Statistical issues, such as designs for which these factors will be discernible and tests of fit, are discussed.
Affective disorders: Evaluation of a three‐allele model accounting for clinical heterogeneity
Authors: Sandkuyl Lodewijk A. , Ott Jurg 
Published: June 2005

AbstractThe group of major affective disorders is clinically heterogeneous. In the genetic linkage study of the Old Order Amish [Egeland et al., 1987] the same disease gene appears to be responsible for the occurrence in one family of several clinically variant forms of affective disorders. Apparently other genetic or environmental factors determine the clinical presentation of this disease gene. We evaluated a three‐allele model where the clinical expression of the disease allele is determined by the other allele at the same locus. In the presence of a proposed modifying allele the disease allele is expressed as major depression, in the presence of the normal (neutral) allele as bipolar disorder (I or II). We applied this model in our analysis of the Old Order Amish data. In analysis of linkage between the locus for affective disroders and two DNA markers on chromosome 11p, we obtained considerably higher likelihood values under the three‐allele model than under a comparable two‐allele model. Also, lodscores were higher under the three‐allele model, with differences in lodscores between both models ranging from 0.95 to 1.34.
Relationship between body mass index, cigarette smoking, and plasma sex steroids in normal male twins
Authors: Meikle A. Wayne , Bishop D. Timothy , Stringham John D. , Ford Marilyn H. , West Dee W. , Rao D. C. 
Published: June 2005

AbstractSmoking has been observed to affect plasma sex hormones and body mass index. The relationship between smoking, body mass index, and plasma concentration of sex hormones was studied in normal adult male twins. The analyses were performed for between 150 and 159 twin pairs for whom hormonal data were available on both twins. With bivariate analysis, neither body mass index nor smoking affected estrone, luteinizing hormone, follicle‐stimulating hormone, ratio of testosterone to estradiol, or ratio of testosterone to dihydrotestosterone. Body mass index significanly (P < 0.05) affected sex hormone binding globulin, whereas smoking had no effect. The plasma contents of testosterone and dihydrotestosterone and the luteinizing hormone/testosterone ratio were affected by both body mass index and smoking, although, after allowing for body mass, smoking was less significant (0.05 < P < 0.10). A path model was formulated to examine the relationship of body mass and sex steroid levels. Our results suggest that body mass index affects sex steroids, since common environmental factors do not account for the strength of the relationship. The bivariate analysis suggests that the smoking effect on sex hormones (except perhaps for dihydrotestosterone) is secondary to an effect on body mass index.
Modeling the age‐of‐onset function in segregation analysis: A causal scheme for leprosy
Authors: Abel Laurent , Mallet Alain , Demenais Florence , Bonney George E. , Rao D. C. 
Published: June 2005

AbstractSeveral methods have been proposed to take into account the variable age of onset of a disease in genetic analysis. A different approach is presented from an etiological point of view. To illustrate the method, we used leprosy, an infectious disease with a variable age of onset depending on both the time of contamination with the bacillus and the latency of the disease; the role of a major gene in the susceptibility to this disease has been recently detected. The age‐of‐onset function was modeled to account for the two temporal processes: contamination event and incubation period. For genetic analysis, this function was combined with the probability of being susceptible to the disease, which was expressed by the use of regressive models. To test this new approach, ten sets of 500 nuclear families were simulated considering different hypotheses of contamination risks, which were either constant or dependent on contacts with contagious leprosy patients, and varying the extent to which the disease is heritable. Analyses of these data using two versions of the model indicate that the model can detect familial correlations in variable age of onset and discriminate between the different simulated effects.
Predicting intrauterine growth reterdation in sibships while considering maternal and infant covariates
Authors: Yang Ping , Beaty Terri H. , Khoury Muin J. , Liang Kung‐Yee , Connolly Margaret A. , Rao D. C. 
Published: June 2005

AbstractData on 6,210 full‐term sibships (gestational age > 36 weeks) reconstructed from birth certificates registered in Maryland between 1980 and 1984 were used to study sibship aggregation and recurrence risk of intrauterine growth retardation (IUGR) while considering maternal and infant covariates. In this study, IUGR was defined as being below the 10th percentile for race‐, sex‐, and gestational‐age‐specific birth weight based on all births registered in Maryland during 1984. Maternal factors (race, age at delivery, marital status, amount of prenatal care, concurrent illnesses, and complications during pregnancy) and infant factors (congenital malformations and first born child or not) were used as covariates in a modified logistic regression model which allowed correlation among sibs. First‐time mothers who were under age 30 years, unmarried, received too little prenatal care, or had any reported pregnancy complications were at high risk of delivering an infant with IUGR. Even given the effects of these risk factors, however, there was a significant correlation in risk among full sibs (r = .237 $ .028), which, combined with information on risk factors, can be used to estimate sibling recurrence risk for IUGR.
Inferences on the inheritance of congenital anomalies from temporal and spatial patterns of occurrence
Authors: Barbujani Guido , Russo Antonella , Farabegoli Alessandra , Calzolari Elisa , Rao D. C. 
Published: June 2005

AbstractMost congenital anomalies are believed to result from interactions between genetic and environmental determinants, whose relative importance is not generally established. Temporal and spatial patterns allow inferences on the underlying transmission processes; in particular, it is possible to discriminate between sporadic and nonsporadic genetic factors, and to find evidence for the effects of environmental heterogeneity in time and space. We studied the occurrence of 14 anomalies in 14 registries of Western Europe. Four basic patterns have been identified: (1) Chromosomal abnormalities have uniform incidences and do not show significant geographical variation, in agreement with the expected consequences of randomly scattered nondisjunction events. (2) The homogeneous spatial distributions of three severe malformations (renal agenesis, oesophageal atresia, ano‐rectal atresia) are consistent with both the effects of fresh mutation and segregation of detrimental alleles. (3) A decrease of similarity of incidences with distance has been observed for neural tube defects, and this is the expected consequence of isolation by distance on genetically determined traits. (4) For facial clefts, polydactyly, and hypospadias, all postulated processes poorly account for the observed temporal and spatial patterns.
Cardiovascular risk factors in a french canadian population: Resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates
Authors: Rice Treva , Vogler George P. , Pérusse Louis , Bouchard Claude , Rao D. C. , Williams Roger R. 
Published: June 2005

AbstractGenetic and environmental influences on systolic (SBP), diastolic (DBP), and mean arterial (MBP) blood pressure were examined using an expanded version of a path model in which parents and their singleton, twin, and adopted offspring were incorporated, and which also included an environmental index as an estimate of the underlying familial environmental component. Estimates of genetic heritability are lower in parents (10–15%) than in offspring (40–50%). Cultural heritability was significant for SBP (0.31) and MBP (0.40), and an intergenerational effect was found for DBP, with higher estimates in parents (0.42) than in offspring (0.21). Marital resemblance was significant, and no support was found for differential maternal and paternal cultural transmission. Two novel results arising from this study are 1) gender‐specific sibling effects, with greater female than male resemblance for SBP and MBP and the opposite pattern for DBP, and 2) the suggestion of extra twin resemblance arising on account of additional shared environments and resulting in greater like‐sex than opposite‐sex twin resemblance. The major conclusions drawn from this study are that 1) parameter estimates are stable with or without the use of extensive environmental indices, and 2) the addition of twins and adoptees did not significantly impact the results, with the exception of a possible influence of the adoptees in estimates of cultural heritability for DBP. Combining both these features (i.e., extended relatives and environmental indices) enables testing for additional sources of familial aggregation, which is not possible using the traditional nuclear family approach and results in a more accurate assessment of the relative roles of heredity and environment on blood pressure than has been previously possible.
Criteria for onset critically influence the estimation of familial risk in Alzheimer's disease
Authors: Breitner John C. S. , Magruder‐Habib Kathryn M. , Rao D. C. , Voglera G. P. 
Published: June 2005

AbstractThe rare early‐onset variant of Alzheimer's disease (AD) appears to be transmitted as an autosomal dominant genetic trait. More typical late‐onset AD also shows familial aggregation, but possible genetic mechanisms are difficult to examine because the phenotypic expression of the putative AD genotype is often censored by prior death from competing causes. Lifetable methods have been used to examine the age‐specific risk of dementia among relatives, and thus to test the hypothesis of genetic transmission of late‐onset AD. These methods require the ascertainment of affected relatives and the determination of their age at onset. The latter determination is somewhat arbitrary, since symptoms of AD evolve and develop in a continuous and progressive fashion, and different workers may thus use differing criteria for “onset.” This paper demonstrates that the use of divergent thresholds for “caseness” (typically, progressive dementia of several years' duration) and onset (e.g., the first appearance of mild cognitive symptoms, or the first clear evidence of dementia) can introduce substantial bias toward underestimation of risk among relatives. Depending on the definition of onset, familial risk may be underestimated, with apparent cumulative incidence decreased to only 60% of values otherwise expected. We suggest that this problem can be avoided by the use of identical threshold criteria for caseness and for onset.
On the measurement of susceptibility to genetic factors
Authors: Khoury Muin J. , Flanders W. Dana , Rao D. C. , Vogler George P. 
Published: June 2005

AbstractGeneticists usually measure the phenotypic effects of a single gene trait in terms of penetrance and recurrence risks in relatives of affected individuals, while epidemiologists usually compute measures of relative and attributable risks. These concepts can be merged to measure the proportion of individuals “susceptible” to a genetic factor. In the context of a sufficient cause model, susceptibility can be defined as the underling factor(s) sufficient to make a person develop disease because of the genetic factor in the absence of other causes. The proportion of susceptibles to the genetic factor in the population differs conceptually and often arithmetically from the penetrance of the genotype especially for common diseases with etiologic heterogeneity. For a wide range of disease and allele frequencies, it can be shown that the proportion of susceptibles can be approximated by the risk difference measure (i.e., difference between penetrance with the genotype and penetrance without the genotype). We also apply the concept of susceptibility to estimate familial recurrence of disease due to a genetic factor. This measure of familial recurrence differs conceptually from simple recurrence risk and can be approximated by the familial risk difference measure (i.e., difference between recurrence risks in relatives of cases and relatives of controls) for a wide range of disease and allele frequencies.
Genetic linkage and complex diseases, with special reference to psychiatric disorders
Authors: Risch Neil , Rao D. C. 
Published: June 2005

AbstractRecent linkage findings for psychiatric disorders, in particular schizophrenia, manic‐depression, and Alzheimer disease, have raised a number of important conceptual issues regarding the genetic etiology of these diseases, as well as the appropriate interpretation of linkage results in studying complex diseases. Perspectives on mode of inheritance, genetic heterogeneity, and phenotypic variation are given.
Transmission of a psychometric indicator for liability to schizophrenia in normal families
Authors: Moldin Steven O. , Rice John P. , Gottesman Irving I. , Erlenmeyer‐Kimling L. , Sing C. F. 
Published: June 2005

AbstractThe genetic analysis of schizophrenia would be facilitated by identification of a heritable correlate of liability. Deviance on an index of Minnesota Multiphasic Personality Inventory (MMPI) signs is associated with the disease phenotype; the familial aggregation and mode of transmission of this continuous psychometric indicator have yet to be established. In this paper, we examine the indicator through commingling analysis and segregation analysis with both the mixed and unified models on 65 nuclear families containing 211 normal individuals. Evidence for a high degree of familiality is found. Analysis of untransformed data under a conditional likelihood provides evidence for Mendelian transmission of a major gene with commingling of two distributions. The frequency of the “high index score” allele is 0.15, with the gene accounting for 31% of the total population variance; such a locus would be relevant to the study of psychopathology as 28% of the population would carry at least one deviant allele. When power‐transformed scores are used to eliminate skewness, there is evidence for one distribution and it is not possible to distinguish single gene from multifactorial (polygenic or cultural) inheritance. While our findings regarding mode of transmission must be interpreted cautiously and confirmation of a single locus requires further study, demonstration of familiality warrants continued investigation of the index as an indicator of liability for schizophrenia.
Structure of ischemic heart disease risk factors in the North Khanty population of Western Siberia
Authors: Puzyrev V. P. , Lemza S. V. , Rao D. C. 
Published: June 2005

AbstractThe relationships between serum lipids, blood pressures, anthropometric traits, age, and ischemic changes of the electrocardiogram (ECG) in the North Khanty population were studied. To this end, eight morphophysiological variables—presumably risk factors for ischemic heart disease—have been subjected to a principal components analysis. Two principal components were extracted. The first revealed age dependency of the traits not associated with ischemic changes of myocardium in both sexes. A comparative analysis of the second component has shown that the chosen traits correlated with ischemic heart disease in males but not in females. Interpretation is given of the components obtained.
Twin concordance for a binary trait: III. A bivariate analysis of hay fever and asthma
Authors: Hopper John L. , Hannah Murray C. , Macaskill Gregory T. , Mathews John D. , Rao D. C. 
Published: June 2005

AbstractSelf‐reported histories of hay fever and asthma were obtained from 3,808 pairs of adult twins 18 years and over registered with the Australian National Health Medical Research Council Twin Registry (1232 MZF, 567 MZM, 751 DZF, 352 DZM, 906 DZO). The prevalence of hay fever and asthma was 0.32 and 0.13, respectively, with little variation with zygosity, sex, and age. The associations between twin pairs for these two traits were analysed, under the assumption of constant prevalences, as a special case of a log‐linear model for binary traits in pedigrees using the statistical package GLIM. The model assumption that there are no secondor higher‐order interactions was tested in the 2 × 2 × 2 × 2 table of twin by disease outcomes without revealing strong evidence of departure, even in this large data set. The log‐linear modelling showed that only three first‐order interactions, namely 1) between hay fever in a twin pair, 2) asthma in a twin pair, and 3) hay fever and asthma in the same twin, were necessary to describe the data. The first two interaction terms were significantly larger in identical pairs; the third was independent of zygosity. Under this parsimonious model, there was a significant difference between identical and fraternal pairs in marginal correlation, both in asthma and hay fever, and in the cross‐correlation between hay fever in one twin and asthma in the other. This suggests that genetic factors are implicated in both hay fever and asthma and that some of these genetic factors are common (at least among a subgroup of individuals) to both traits.
Estimating familial effects on age at onset and liability to schizophrenia. II. Adjustment for censored data
Authors: MacLean Charles J. , Neale Michael C. , Meyer Joanne M. , Kendler Kenneth S. , Rao D. C. 
Published: June 2005

AbstractGenetic studies of disorders with adult onset often contain individuals who have not completed their age at risk when last observed. Without correction for such censoring, correlation in ages at onset among relatives is substantially underestimated. Moreover, without correction for the effect of correlated ages at onset, the relationship between age at onset in the proband and liability in relatives is substantially overestimated. The present paper describes methods for correcting the effects of censoring on these estimates. In a companion paper [Kendler and MacLean,Genet Epidemiol7:409–417, 1990] these methods are applied to a large family study of schizophrenia.
Heritability of blood pressure in 7‐ to 12‐year‐old Chinese twins, with special reference to body size effects
Authors: Wang Zhiqiang , Ouyang Zhen , Wang Dongmei , Tang Xilin , Rao D. C. 
Published: June 2005

AbstractSystolic and diastolic blood pressures and body‐size indices such as body height, body weight, sitting height, chest circumference, skinfold thickness, and body mass index (BMI) were assessed in 110 pairs of like‐sex Chinese twins (75 monozygotic and 35 dizygotic) aged 7–12 years. Significant correlations of blood pressure with body‐size indices were found. Prior to adjusting for body‐size effects, three twin methods yielded low heritability estimates for both systolic (0.32–0.41) and diastolic (0.32–0.51) pressures. Adjusting systolic pressure for body height and BMI via multiple regression nearly halved heritability estimates, but adjusting diastolic pressure for body height and skinfold thickness only changed the estimates slightly.