bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using multidimensional scaling on data from pairs of relatives to explore the dimensionality of categorical multifactorial traits
Authors: Meyer J. M. , Heath A. C. , Eaves L. J. , Chakravarti A. 
Published: June 2005

AbstractAn accurate specification of the dimensionality and ordering of categorical multifactorial phenotypes (e.g., smoking status, including heavy, moderate, light, and nonsmokers) is an important prerequisite for the genetic analysis of these traits. Typically, phenotypic dimensionality and ordering are determined by comparing the relative fits of alternative parametric threshold models. Here, a method of analysis is described which addresses the same issue of trait dimensionality but does not require parametric assumptions. Specifically, we detail how nonmetric multidimensional scaling (MDS), applied to contingency tables which cross‐classify the phenotypes or responses of one relative with another, may be used to explore trait dimensionality. Scaling results from deterministic simulation studies indicate that the latent structure of categorical phenotypes can be recovered with nonmetric MDS. Results from stochastic simulations, however, indicate that the accuracy of recovery, as well as the rejection of models of incorrect dimensionality, are strongly dependent upon sample size and the latent liability correlation between relatives. As an application of the method, the dimensionality of a measure of smoking status in 1,656 pairs of monozygotic twins ascertained through the American Association of Retired Persons is considered. The MDS results indicate that the onset of the smoking habit and the quantity smoked in this aging population represent a unidimensional process. The implication this finding has for subsequent genetic analysis is discussed. © 1992 Wiley‐Liss, Inc.
Specificity and sensitivity of hexosaminidase assays and DNA analysis for the detection of tay‐sachs disease gene carriers among Ashkenazic Jews
Authors: Fernandes Maria J. G. , Kaplan Feige , Clow Caroline L. , Hechtman Peter , Scriver Charles R. , Mulvihill John. J. 
Published: June 2005

AbstractTay‐Sachs disease (TSD), a neurodegenerative disorder resulting from a deficiency of the lysosomal enzyme hexosaminidase A (HexA), clusters in Ashkenazic Jews. Population‐based screening programs to detect carriers of TSD genes by means of HexA assays have been active since the 1970s. The recent characterization of 3 mutations in the HEXA gene (in exon 7, exon 11, and intron 12), which account for over 90% of HEXA mutations in Ashkenazim, appeared to offer better options for screening and diagnosis. The relative frequencies of the three mutations in Montreal are similar to those reported in four other North American populations. We compared enzyme and DNA analyses to determine specificity and sensitivity of each test when the other was used as the confirmatory procedure. Neither procedure has a sensitivity of 1.0. Maximum sensitivity and specificity were achieved by using both tests together. The findings here are likely to apply to most cases where the variant screened enzyme phenotype can result from more than one mutation. © 1992 Wiley‐Liss, Inc.
Genetic analysis of drinking behavior in World War II veteran twins
Authors: Carmelli Dorit , Heath Andrew C. , Robinette Dennis 
Published: June 2005

AbstractThe objective of the present study was to investigate longitudinal changes in drinking behaviors of adult male twins and model these changes as a function of genetic and environmental influences. Alcohol data available for World War II veteran twins, first surveyed in 1967–69 and followed up during 1983–85, were used to examine components of variability in measures of alcohol consumption. Multivariate biometric analyses of these data indicated 1) longitudinal stability of drinking behaviors in this cohort, 2) a significant contribution of genetic factors to the observed stability that accounted for more than 80% of the stable variation in frequency and in quantity of alcohol consumed per drinking occasion, and 3) evidence for a significant contribution of shared environmental influences to drinking of specific beverages (e.g., wine). The implications of these results for issues of health in the elderly are considered. © 1993 Wiley‐Liss, Inc.
Labman and Linkman: A data management system specifically designed for genome searches of complex diseases
Authors: Adams Phillip 
Published: June 2005

AbstractTwo programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker‐allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user‐specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports.The programs include features critical for conducting genome searches of complex diseases: They are easy‐to‐use, well‐tested, and reliable. Data from multi‐center investigations can be easily combined for analysis. Moreover, they include extensive error‐checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS. © 1994 Wiley‐Liss, Inc.
Segregation analyses of four urinary caffeine metabolite ratios implicated in the determination of human acetylation phenotypes
Authors: Vincent‐Viry Monique , da Silva Pontes Zelia Braz Vieira , Gueguen René , Galteau Marie‐Madeleine , Siest Gérard 
Published: June 2005

AbstractHuman acetylation phenotypes were determined with caffeine (137X) as the test substance, improved by measuring urinary caffeine metabolites with a previously described HPLC method. Caffeine, 5‐acetylamino‐6‐formylamino‐3‐methyluracil (AFMU), 1‐methylxanthine (1X), 1‐methyluric acid (IU), 1,7‐dimethylxanthine (17X), and 1,7‐dimethyluric acid (17U) were quantified. This study tested the hypothesis, suggested by previous studies, that the acetylation polymorphism is strongly influenced by a major gene. Phenotypes were assessed by using four urinary caffeine metabolite ratios: AFMU/1X, AFMU/[1X + 1U + 17U], AFMU/[AFMU + 1X + 1U], and AFMU/[1X + 1U + 17X + 17U] in a population included 281 nuclear family members who were healthy volunteer subjects. Each urinary ratio revealed strong familial aggregation with correlations between parents and offspring varying from 0.340 to 0.486 as a function of the ratio considered, and between sibs from 0.410 to 0.512 whereas correlations among spouses were not significant, excluding an effect of environmental factors. Segregation analyses were conducted upon these four ratios testing a series of specific models of inheritance and gave evidence for single locus control of N‐acetyltransferase (NAT) activity, with Mendelian codominant transmission using the AFMU/1X, AFMU/[1X + 1U + 17U], and AFMU/[1X + 1U + 17X + 17U] ratios. The slow allelic frequencies were 0.739, 0.753, and 0.724, respectively, and the phenotypic concordance was 90 to 92% with the AFMU/1X ratio. The familial aggregation observed in using the AFMU/[AFMU + 1X + 1U] ratio was consistent with a recessive transmission for the allele controlling the homozygous slow phenotype. This last ratio is not convenient to differentiate rapid heterozygous and homozygous phenotype. Considering the number of misclassified subjects, this study would be completed by genotyping the same families as demonstrated by some authors who predicted 97.5% of acetylation phenotype when using PCR‐based DNA amplification test. © 1994 Wiley‐Liss, Inc.
Recurrence risk for major congenital heart defects in Sweden: A registry study
Authors: Pradat Pierre 
Published: June 2005

AbstractDuring the period 1981–1986, 1605 infants presenting a major congenital heart defect (CHD) were identified in Sweden. Using the personal identification numbers of the mothers, 1507 of them could be linked to the Medical Birth Registry and two controls were selected for each infant. For this total of 4521 infants, 2686 postoccurrence sibs born during the period 1981–1989 were identified from the Medical Birth Registry. The tendency to have one or more sibs was higher among cases than among controls and was correlated to the life status of the proband. This tendency did not vary according to the type of CHD when controlling for life status. The prevalence at birth of CHD was almost four times higher among sibs of CHD infants than among sibs of normal infants. The tendency to have a sib with an extracardiac malformation did not differ between CHD probands and normal probands. The importance of only including births occurring after the proband when evaluating recurrence risks is stressed. © 1994 Wiley‐Liss, Inc.
Comparative epidemiology of selected midline congenital abnormalities
Authors: Yang Ping , Khoury Muin J. , Stewart Walter F. , Beaty Terri H. , Chee Elsbeth , Beatty Jennifer C. , Diamond Earl L. , Gordis Leon 
Published: June 2005

AbstractWe present comparative epidemiologic characteristics of five congenital abnormalities that have been suggested to result from midline abnormal developmental disturbances: esophageal atresia with or without tracheoesophageal fistula (EA/TEF), imperforate anus with or without fistula (IA/F), omphalocele (OM), bladder exstrophy (BE), and diaphragmatic hernia (DH). The purpose was to assess the extent of epidemiologic similarities among these five defects. Data were collected as part of a population‐based case‐control study of infants with these defects born to mothers residing in Maryland, Washington, D.C., or Northern Virginia from 1980 through 1987. The estimated annual birth prevalences (per 10,000 live births) and 95% confidence intervals (CI) of these five defects were 0.40 (0.26–0.61) for BE, 1.34 (1.08–1.67) for OM, 1.59 (1.29–1.95) for DH, 2.11 (1.76–2.53) for EA/TEF, and 2.97 (2.55–3.46) for IA/F. The birth prevalence of IA/F and DH increased between 1980 and 1987. In contrast to the other four defects, DH showed a significant male preponderance (rate ratio 1.57, 95% CI 1.03–2.47), a significant white excess (rate ratio white:other, 1.56, 95% CI 1.00–2.48), and a lower proportion of multiple associated defects (30% vs. 46–61%). We concluded from this study that the descriptive epidemiology of diaphragmatic hernia is different from that of the other four defects. This finding may imply differences in etiologic and pathogenetic mechanisms underlying DH. © 1994 Wiley‐Liss, Inc.
Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in chinese non‐smokers
Authors: Saha N. , Tay J. S. H. , Low P. S. , Humphries S. E. 
Published: June 2005

AbstractThe influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at −75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high‐density lipoprotein cholesterol (HDLC) and apo AI and lower low‐density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy‐Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24–0.31] than that reported in Caucasians (0.12; 95% CI 0.09–0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non‐smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits. © 1994 Wiley‐Liss, Inc.
Genetic influences on age‐related change in total cholesterol, low density lipoprotein‐cholesterol and triglyceride levels: Longitudinal apolipoprotein E genotype effects
Authors: Jarvik Gail Pairitz , Austin Melissa A. , Fabsitz Richard R. , Auwerx Johan , Reed Terry , Christian Joe C. , Deeb Samir 
Published: June 2005

AbstractThis study addressed the possible influence of apolipoprotein E (apo E) genotype on age‐related changes in total cholesterol (TC), low density lipoprotein‐cholesterol (LDL‐C), and triglyceride (TG) levels in older males. Apo E is a component of LDL, is a ligand for the LDL receptor, and apo E genotype has been consistently associated with variation in mean levels of TC and LDL‐C, and also appears to influence TG levels. Using male twins followed longitudinally between mean ages of 48 and 63 years, the change in TC, LDL‐C, and TG over time for individuals with the ϵ3ϵ3 and the ϵ3ϵ4 genotypes was contrasted. At exam 1 mean TC and LDL‐C levels were lower in the ϵ3ϵ3 group than in the ϵ3ϵ4 group, but at exam 3 mean TC and LDL‐C levels were significantly higher in the ϵ3ϵ3 group than in the ϵ3ϵ4 group. The rate of change in TC and LDL‐C with age differed significantly between ϵ3ϵ3 and ϵ3ϵ4 groups. Results for TG were not statistically significantly. These findings suggest that the apo E genotype effects on risk of coronary artery disease may be age‐dependent. This study demonstrates the value of longitudinal studies in refining models for genetic risk factors for disease. © 1994 Wiley‐Liss, Inc.
Familial aggregation of cardiovascular diseases in African‐American pedigrees
Authors: Rotimi Charles , Cooper Richard , Cao Guichan , Sundarum Callie , McGee Daniel 
Published: June 2005

AbstractFamilial aggregation of cardiovascular diseases and diabetes has been consistently demonstrated. However, virtually all of the evidence on the familial patterns of these diseases has come from white population samples. This study evaluates the level of familial excess risk among first degree relatives of 232 African‐American pedigrees which included 1,420 individuals recruited from the Chicago, IL, area. Excess disease risk was observed among relatives (parents and offsprings) of affected probands compared to relatives of unaffected probands for coronary heart disease (odds ratio [OR] = 5.30; 95% confidence interval [CI] = 2.51–11.23); hypertension (OR = 1.98; CI = 1.41–2.80); stroke (OR = 3.24; CI = 1.08–9.70); and diabetes (OR = 2.95; CI = 1.55–5.62). The results of this study clearly show that coronary heart disease, hypertension, stroke, and diabetes aggregate in some African‐American families and not others. Unaffected relatives of persons suffering from these diseases should be encouraged to have their blood pressure, lipid, and blood glucose levels measured at frequent intervals. These recommendations are particularly urgent in African‐American communities because of the disproportionately high morbidity and mortality experienced from cardiovascular diseases and diabetes. © 1994 Wiley‐Liss, Inc.
Inferring the direction of causation in cross‐sectional twin data: Theoretical and empirical considerations
Authors: Duffy David L. , Martin Nicholas G. 
Published: June 2005

AbstractA recent multivariate extension of the classical twin study in theory allows the inference of the direction of causation between correlated traits solely using cross‐sectional data. In this paper we briefly review this model and assess its usefulness by applying it to a number of pairs of biological and psychological variables between which the nature of the causative relationship is already known. We conclude that the method has a number of biases and limitations. If a causative relationship at the phenotypic level exists between two traits, the correct direction of causation is usually identifiable, providing the reliability and validity of the measures are known. Failure to correctly specify a measurement model can lead to incorrect tests of hypotheses. Difficulties can also occur when discriminating between a direct causative relationship and a correlation due to common genetic or environmental determinants, but these occur in predictable situations. If these considerations are taken into account in interpretation of results, the true nature of the association between traits can often be correctly identified, or at least included in a subgroup of best fitting models. © 1994 Wiley‐Liss, Inc.
Epidemiology of retinitis pigmentosa in the valencian community (Spain)
Authors: Nájera C. , Millán J. M. , Beneyto M. , Prieto F. 
Published: June 2005

AbstractThe purposes of this study are to determine the frequencies of the different genetic forms of retinitis pigmentosa and to perform segregation analysis in the different genetic subtypes. Retinitis pigmentosa was diagnosed in 263 persons from 132 families. The frequency of the autosomal recessive type was the highest (31.8%) while the X‐linked type was very rare (1.5%). The frequency of autosomal dominant type was 14.4% and the simplex cases constituted half of the total cases of RP registered in our community. In conclusion, in our population the high proportion of simplex cases and the low number of X‐linked families are noticeable. The result of segregation analysis showed good agreement with expectation in autosomal dominant and autosomal recessive families but no more than 60% of all simplex cases were autosomal recessive. The proportion of sporadic cases was estimated statistically to be 39.9% of the total simplex cases. © Wiley‐Liss, Inc.
Apolipoprotein E4 allele and Alzheimer disease: Examination of Allelic association and effect on age at onset in both early‐and late‐onset cases
Authors: Locke P. A. , Conneally P. M. , Tanzi R. E. , Gusella J. F. , Haines J. L. 
Published: June 2005

AbstractAn increased frequency of the apolipoprotein E type 4 allele (APOE‐4) has previously been associated with both late‐onset sporadic and late‐onset familial Alzheimer disease (AD) [Strittmatter et al. (1993) Proc Natl Acad Sci USA 90:1977–1981; Saunders et al. (1993a) Neurology 43:1467–1472]. To further investigate this association we genotyped affected individuals from 92 separate AD pedigrees including both early‐ and late‐onset cases. An increased frequency of the APOE‐4 allele was found only among the late‐onset cases, both familial and sporadic, confirming the earlier reports. In addition, age at onset was significantly decreased in the APOE‐4 homozygotes (in late onset families) compared to either APOE‐4 heterozygotes or individuals not carrying an APOE‐4 allele. We also observed a significantly decreased frequency of the APOE‐2 allele in both the early‐and late‐onset familial cases. These results strengthen the argument for a direct role of APOE in susceptibility to AD. © Wiley‐Liss, Inc.
Statistical validity for testing associations between genetic markers and quantitative traits in family data
Authors: Nick Todd G. , George Varghese , Elston Robert C. , Wilson Alexander F. 
Published: June 2005

AbstractIn genetic analysis it is often of interest to analyze associations between traits of unknown genetic etiology and genetic markers from pedigree data. Statistical methods that assume independence of pedigree members cannot be used because they disregard the statistical dependencies of members in a pedigree. For quantitative traits, a regression model proposed by George and Elston [Genet Epidemiol 4:193–201, 1987] uses an asymptotic likelihood ratio test and incorporates a correlation structure that allows for statistical dependence among the pedigree members. The statistical validity of this test is assessed for finite samples by measuring the discrepancy between the empirical and theoretical chi‐square distributions. The variance of the mean of the dependent variable is determined to be related to this discrepancy and can be used to determine whether a pedigree structure is large enough for making valid statistical inferences on the basis of the asymptotic test. A multi‐generational pedigree of 200 or so individuals should in many cases be sufficient for valid results when using the asymptotic likelihood ratio test for the association between markers and continuous traits. © 1995 Wiley‐Liss, Inc.
Asymptotic distributions of polylocus test statistics
Authors: Goldstein Darlene R. 
Published: June 2005

AbstractPolylocus linkage analysis methods are modified two‐point analyses which aim to approach the information gain of multilocus analysis. Terwilliger and Ott [(1992) Am J Hum Genet 51:A202, (1993) Genet Epidemiol 10:477–482] put forth two such methods. This paper presents asymptotic approximations to the null distribution of the likelihood ratio statistics for these two methods, correcting earlier reports [Terwilliger and Ott (1993) Genet Epidemiol 10:477–482; Schaid and Elston (1994) Genet Epidemiol 11:1–17]. The performance of the approximations is then assessed for finite samples of fully informative meioses. © 1995 Wiley‐Liss, Inc.
Statistical methodology for estimating twin similarity with respect to a dichotomous trait
Authors: Donner Allan , Klar Neil , Eliasziw Michael 
Published: June 2005

AbstractStatistical methodology is presented for the estimation of twin similarity with respect to a dichotomous trait. The methodology focuses on the intraclass correlation as the parameter of interest and is analogous to methodology commonly applied to continuous outcome data. For inference problems involving a single sample, confidence interval construction and significance testing are discussed. For two sample problems, test procedures are provided that are an alternative to an approach recently presented by Ramakrishnan et al. [(1992) Genet Epidemiol 9:273–287 (1)]. Two examples based on published data sets are given to illustrate the proposed techniques. ©1995 Wiley‐Liss, Inc.