bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of a Pvull RFLP at the lipoprotein lipase locus with fasting insulin levels in Hispanic men
Authors: Cole S. A. , Aston C. E. , Hamman R. F. , Ferrell R. E. 
Published: June 2005

AbstractWe present results from an association study between RFLPs in the lipoprotein lipase (LPL) gene and lipid and insulin levels. The study population consisted of 102 Hispanic men and 97 Hispanic women. The subjects were genotyped for two previously reported RFLPs detected with the restriction enzymes HindIII and PvuII. The frequencies of the RFLPs in the Hispanic population are similar to those seen in other Caucasian populations. Strong linkage disequilibrium was detected between the sites in Hispanics. Genotypes were used separately in analyses of variance with fasting serum triglycerides, total cholesterol, high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, HDL2/HDL3‐cholesterol, and insulin levels, as well as two measures of adiposity: waist‐hip ratio and body mass index. Men and women were analyzed separately. Mean fasting insulin levels of the LPL PvuII genotypes were significantly different from each other in Hispanic men. The mean fasting insulin level of men who were homozygous for the presence of the PvuII site (+/+) was 9.20 ± 0.24 μunits/ml, men who were heterozygous had a mean level of 10.54 ± 0.20 μunits/ml, and men who were homozygous for the absence of the site (‐/‐) had a mean of 12.91 ± 0.30 μunits/ml. This effect was not seen in Hispanic women. These results suggest that the regulation of LPL by insulin may be different in Hispanics with different LPL PvuII genotypes. © 1993 Wiley‐Liss, Inc.
Segregation analysis of autosomal dominant polycystic kidney disease
Authors: Dobin A. , Kimberling W. J. , Pettinger W. , Bailey‐Wilson J. E. , Shugart Y. Y. , Gabow P. 
Published: June 2005

AbstractThe results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95 % of autosomal dominant PDK (ADPKD) families have PKD 1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any segregation distortion and to obtain new estimates of the age‐dependent penetrance. Penetrance at the early ages of onset has increased during the last decade, presumably because of improvements in renal imaging and consequent earlier age of diagnosis. In the current study, the mean age of diagnosis was estimated to be 20 years, with a standard deviation (SD) of 15.94. Under the best fitting model (autosomal dominant), over 70 % penetrance was estimated by age 30 years, over 95 % by 50 years, and 99 % by 55 years. Thus, diagnosis of this disease at an early age is possible without total reliance on DNA typing. The segregation ratio defined through the transmission probability in our model was not significantly different from 0.50, but its confidence limits were broad: 0.36 to 0.64. Neither transmission probability nor penetrance was significantly influenced by gender. The mutation rate was estimated to be 6.9 × 10−5, in accordance with the previously observed high mutation rate for PKD. However, the mutation rate in our study may be overestimated because it neglects low penetrance alleles and phenocopies. © 1993 Wiley‐Liss, Inc.
Some empirical properties of an all‐relative‐pairs linkage test
Authors: Olson Jane M. 
Published: June 2005

AbstractOlson and Wijsman [Genet Epidemiol 10:87–102, 1993] recently proposed a single test of linkage which combines information from different types of relative pairs in a pedigree. Relative‐pair‐type‐specific regression parameters that relate the squared pair trait difference to the estimated number of marker genes shared identical by descent between the pair are estimated using generalized estimating equation methodology, then combined to give a single linkage test statistic. Questions remain concerning the small sample and robustness properties of this test statistic; these questions are addressed in the present paper using simulation. The test is substantially anti‐conservative for samples with fewer than about ten families and are approximately valid for samples larger than about 15 families. In addition, the test appears robust in the presence of trait genotype by environment interaction, trait family‐specific errors, a second major trait locus, and trait dominance. Surprisingly, the sibpair test was more powerful than the all‐relative‐pairs test for dominant traits with high heritability. Finally, adjusting for the presence of a marker known to be linked to one trait locus only marginally improves the power for detecting a second trait locus. © 1994 Wiley‐Liss, Inc.
Sources of variability of human plasma apolipoprotein A‐IV levels and relationships with lipid metabolism
Authors: Zaiou Mohamed , Visvikis Sophia , Gueguen René , Steinmetz Josiane , Parra Henri‐Joseph , Fruchart Jean‐Charles , Siest Gérard 
Published: June 2005

AbstractPlasma apolipoprotein (apo) A‐IV concentration was determined by immunoelectrophoretic assay (EIA) in 119 nuclear families. No significant effect of concomitants such as age, weight, height, body mass index, tobacco, and alcohol consumption was observed on apo A‐IV levels in men and in boys. In women, contraceptive use and hormonal status affected apo A‐IV levels. In girls, only age influenced the quantitative phenotype. After adjusting by specific concomitants significant correlations were observed between apo A‐IV levels and triglycerides, apolipoprotein A‐I and apo B levels, suggesting a role of apolipoprotein A‐IV in the hepatic lipid metabolism. Intrafamilial correlations were estimated to investigate the plausibility of a common family factor. The results obtained in this study showed a significant correlation between family members with the exception of mother‐daughter pairs. Using a variance components model, the contribution of genetic and environmental factors was then investigated. Different statistical models were used and two major hypotheses were statistically acceptable: the first hypothesis supports that shared and specific environmental factors explain 35 and 65%, respectively, of the total adjusted plasma apo A‐IV variation. The fraction of apo A‐IV variability attributable to genetic factors was null. The second hypothesis supports that the fraction of variability attributable to apo A‐IV genetic variation is 67% and the common spouse environmental factors are responsible for 33% of the total variability and no specific environmental effect was found. Among the two hypotheses, taking account of the metabolism function, we support the first one without excluding gene‐ environment interactions which could mask the genetic influence. © 1994 Wiley‐Liss, Inc.
Affected sib pair identity by state analyses
Authors: Thomson Glenys , Motro Uzi 
Published: June 2005

AbstractFour methods using identity by state (IBS) data from affected sib pairs are compared for their ability to detect linkage between a diallelic marker and disease. A joint null hypothesis of no linkage and no linkage disequilibrium between the marker and disease must be considered. Two tests have undesirable properties in the case of linkage disequilibrium. Which of the other two tests has more power is dependent on the presence or not of linkage disequilibrium. The procedure of choice when possible is to type parents of affected sib pairs: the null hypothesis of no linkage can then be tested using identity by descent (IBD) values from informative parents, and the null hypothesis of no marker association with disease (linkage equilibrium) can be tested independently using the marker allele frequencies in the affected sib pairs.
Power of segregation analysis for detection of major gene effects on quantitative traits
Authors: Borecki I. B. , Province M. A. , Rao D. C. 
Published: June 2005

AbstractThe power to detect major gene effects by rejection of the “no major gene” null hypothesis against a mixed model alternative was determined in random samples of nuclear families over a variety of conditions. Benchmarks have been developed using a varying number of families whose structure includes both parents and three children. Phenotypes were simulated assuming a Mendelian major gene under either recessive or dominant inheritance, with 0–30% residual polygenic heritability. Three trait prevalences—5, 10, and 20%—were considered in combination with increasing displacement between homozygous means, spanning a range of 14 to 36% of the phenotypic variance attributable to the major gene effect. All other assumptions of the traditional mixed model were adopted in the generating models. Segregation analysis was carried out on the simulated data sets, and the proportion of samples out of 200 replications in which the null hypothesis q = 0 was rejected is reported as the power. Thus, failure to detect a major gene effect in this context is solely due to sampling variation, since no other perturbations were introduced. In general, there appears to be greater power to detect dominant major gene effects as opposed to recessive ones using otherwise comparable parameter values, and the effect of varying sibship size under dominant models appears to be greater as well. The use of joint vs. conditional likelihood calculations also was evaluated; substantial drops in power were observed when using conditional likelihoods under recessive inheritance, while the differences in power appeared to be nominal under dominant inheritance. The results of this investigation are offered as a guide to assist in the design of family studies whose aim is to detect major gene effects.
Evidence for multiple genes determining sodium transport
Authors: Hasstedt Sandra J. , Hunt Steven C. , Wu Lily L. , Williams Roger R. 
Published: June 2005

AbstractSodium transport comprises a set of interacting systems. Consequently, a defective sodium transport gene affects multiple sodium transport systems, and a sodium transport variable measured on a sample of individuals reflects genetic variation from a number of different genes, complicating the task of identifying the effect of a single gene. To test for genes which affect sodium transport, we first applied principal components analysis to 14 variables related to sodium transport, thereby defining uncorrelated sources of variation in the variables. The sample consisted of 1,218 members of 68 pedigrees ascertained through probands with early‐onset stroke, hypertension, or coronary heart disease. Segregation analysis of the 14 principal components scores provided evidence for 8 genetic variants which alter sodium transport. One of the 8 variants is recessive, has homozygous genotype frequency estimated as 8.8% of the population, and increases sodium‐lithium countertransport, the passive sodium leak, body mass index, and triglyceride; the genetic variant may coincide with an insulin resistance gene. A second of the 8 variants is also recessive, has homozygous genotype frequency estimated as 7.4% of the population, and increases intraerythrocytic sodium and the passive sodium leak while decreasing sodium pump number; the genetic variant may reduce pump number. Two of the 8 variants substantially increase sodium‐lithium countertransport; frequency estimates for heterozygotes for the dominant variant and homozygotes for the recessive variant equal 1.8% and 3.1 %, respectively. Another of the 8 variants is recessive, has homozygous genotype frequency estimated as 1.9%, and increases body mass index. Each of the 3 remaining variants is rare and expressed in less than 1 % of the sample. © 1994 Wiley‐Liss, Inc.
ARCAD: A method for estimating age‐dependent disease risk associated with mutation carrier status from family data
Authors: Le Bihan Christine , Moutou Céline , Brugières Laurence , Feunteun Jean , Bonaïti‐Pellié Catherine 
Published: June 2005

AbstractWe present ARCAD, a method to estimate the disease risk associated with mutation carrier status using data on families ascertained by affected individuals, in which a germline mutation has been detected. Because the event of interest, the age of onset, is a censored variable, the method uses the survival analysis approach to formulate the likelihood. Provided that selection criteria are clearly defined, the ascertainment bias is removed by including a correction term in the likelihood computation. We simulated family data and selected those with a proband affected before age 17, and at least one or at least two relatives affected before age 46. We show that including the correction for the ascertainment provides reliable estimates of the risk, even when many individuals are not tested for the mutation. An application to cancer risk and germline p53 mutations is presented. We routinely investigate the p53 status for all the children treated in the Department of Pediatric Oncology at the Institute Gustave Roussy, whose family displays at least one relative affected by cancer before age 46. We identified 5 families with an inherited germline p53 mutation. The risk for any cancer for a mutation carrier estimated by ARCAD was 42% within the age class 0–16 years, 38% within the age class 17–45 years, and 63% after 45 years, with a lifetime risk of 85%. These risks are almost entirely explained by the occurrence of the six most frequent cancers encountered in the Li‐Fraumeni syndrome. © Wiley‐Liss, Inc.
Sex‐specific effects for body mass index in the new Norwegian twin panel
Authors: Harris Jennifer R. , Tambs Kristian , Magnus Per 
Published: June 2005

AbstractSex‐specific effects for body mass index (BMI) were explored in a newly established, population‐based Norwegian twin panel. The sample includes 5,864 individuals, aged 18–25 years, who responded to a questionnaire containing items for zygosity classification, height, weight, health, health‐related behaviors, well‐being, and demographic information. Among the 2,570 intact pairs who returned the questionnaire there were 416 identical (MZ) male pairs, 387 fraternal (DZ) male pairs, 528 MZ female pairs, 443 DZ female pairs, and 796 unlike‐sexed pairs. Alternate sets of models testing for either sex‐specific genetic or environmental parameters were evaluated using structural equation analysis. Results from the most parsimonious model indicated that the genes contributing to variation in BMI are not identical for men and women; rather, some genetic effects were shared by the sexes and some were unique to each sex. Total variation in BMI could be explained by sex‐specific additive genetic effects, as well as genetic and non‐shared environmental effects common to men and women. Estimates of heritability were .708 for men and .789 for women, and the male‐female genetic correlation was 0.622. The series of models specifying sex‐specific shared environment also fit the data and suggests that shared environmental factors may be important for males but not for females. The findings raise questions concerning the relationship between sex‐specific effects for BMI and sex differences in health outcomes. ©1995 Wiley‐Liss, Inc.
Evaluating a new algorithm for linking maternal and newborn medical records
Authors: Grace Kimberly R. , Waters Grady , Huether Carl A. , Edmonds Lawrence D. , McClain Phillip 
Published: June 2005

AbstractLinking maternal and newborn medical records is a valuable tool for assessing the relationship between maternal variables and fetal outcome. This study evaluated the Center for Disease Control's newly developed maternal and newborn medical record linkage system, a computer program that uses weighted variables to determine the most likely maternal and newborn pairs. Any newborn record not achieving a set minimum score with a maternal record remains nonmatched. The objectives of the study were to estimate the program's matching accuracy, determine causes of incorrect matches and nonmatches, develop suggestions for program revisions, and evaluate the effects of the revisions. The study sample included 521 matched and 247 nonmatched maternal and newborn medical records from seven Ohio hospitals. Of all available newborn records (10,068), 574 (5.7%) did not match with maternal records; for those in which a match occurred, the authors ascertained a 98% matching accuracy and determined explanations for nonmatched and incorrectly matched records. The authors noted a greater prevalence of birth defects and prematurity among newborns with nonmatched records than among those with matched records. Program revisions, therefore, focused on reducing the prevalence of nonmatched records. The revised program reduced the prevalence of nonmatched records from 5.7% to 3% but reduced matching accuracy. ©1995 Wiley‐Liss, Inc.
Epidemiologic and genetic follo‐up study of 544 Minnesota breast cancer families: Design and methods
Authors: Sellers Thomas A. , Anderson V. Elving , Potter John D. , Bartow Susan A. , Chen Ping‐Ling , Everson Lenore , King Richard A. , Kuni Christopher C. , Kushi Lawrence H. , McGovern Paul G. , Rich Stephen S. , Whitbeck Jan , Wiesner Georgia 
Published: June 2005

AbstractIn 1944, a case‐control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing, breastfeeding, and hereditary susceptibility on the occurrence and age‐of‐onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study; for most probands this includes the original tissue blocks.We are conducting a historical cohort study of selected first‐ and second‐degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first‐ and second‐degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non‐genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk.This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non‐genetic exposure determined in at least four generations. ©1995 Wiley‐Liss, Inc.
Major gene with sex‐specific effects influences fat mass in Mexican Americans
Authors: Comuzzie Anthony G. , Blangero John , Mahaney Michael C. , Mitchell Braxton D. , Hixson James E. , Samollow Paul B. , Stern Michael P. , MacCluer Jean W. 
Published: June 2005

AbstractIncreased adiposity has repeatedly been identified as a major risk factor for a variety of chronic diseases. However, the question still remains whether the amount of adipose tissue itself is genetically mediated. To address this question, a segregation analysis, using maximum likelihood techniques as implemented in the computer program Pedigree Analysis Package (PAP), was performed on fat mass (kilograms of body fat) in a large sample of extended Mexican American families residing in San Antonio, TX. The only model not rejected was a Mendelian mixed model for fat mass, incorporating genotype X sex interaction. In males the major gene accounted for 37% of the total variance compared with 43% in females. In both sexes homozygous recessive individuals have a fat mass more than double that of individuals of the other two genotypes. It was possible to reject linkage of the anonymous major gene for fat mass with several candidate loci for obesity. However, tentative evidence of linkage was detected with markers on both chromosomes 2 and 11, thereby providing hypotheses for future testing. ©1995 Wiley‐Liss, Inc.
Underexpression of the apolipoprotein E2 and E4 alleles in the Greek Cypriot population of Cyprus
Authors: Cariolou Marios A. , Kokkofitou Avgousta , Manoli Panayiotis , Christou Soteroula , Karagrigoriou Alexandros , Middleton Lefkos 
Published: June 2005

AbstractApolipoprotein E (APOE) plays an important role in the multifactorial etiology of both cardiovascular disease and Alzheimer's disease. Polymerase chain reaction (PCR) was used to investigate the APOE gene polymorphism in 335 unrelated Greek Cypriots living on the island of Cyprus. For the most common APOE genotypes, the Greek Cypriots followed the general Caucasian European pattern of having higher genotypic frequencies of E3/3, followed by E3/4, and then E2/3. Among the European populations compared, Greek Cypriots exhibited the lowest relative frequency of the E3/4 genotype (12.83%). Also, the relative frequencies of the E2 and E4 alleles in Greek Cypriots were among the lowest around the world (5.4% and 7.0%, respectively). This was also demonstrated by using the complete and the average clustering methods of analysis where the APOE allele relative frequencies in Greek Cypriots were compared to 46 other populations. The Greek Cypriot population in these analyses clustered with populations mainly from south Europe and Japan which have low E2 and E4 allele frequencies. The Greek Cypriot population will be studied further for elucidating the effect(s) and the role of APOE in cardiovascular disease and the APOE4 allele as a possible metabolic factor affecting the rate of expression of both Alzheimer's disease and vascular dementia. ©1995 Wiley‐Liss, Inc.
An oliogenic disease displaying weak marker assocations: A summary of contributions to problem 1 of GAW9
Authors: Hodge Susan E. 
Published: June 2005

AbstractProblem 1 consisted of artificial data simulated from an oligogenic (four‐locus) disease model. The data set contained 200 nuclear families with at least one affected child and 100 control families with no affected members. Two of the disease loci were intended to be detectable via association analysis but not necessarily via linkage analysis, and the other two were virtually undetectable in this data set. Participants used association analysis, linkage analysis, and segregation analysis to analyze these data. Their findings are summarized, and analysis strategies are discussed. ©1995 Wiley‐Liss, Inc.
Genetic analysis workshop 9: Development of problem 1
Authors: Hodge Susan E. 
Published: June 2005

AbstractProblem 1 was designed to involve an oligogenic model with four “disease susceptibility” loci, such that all individuals with at least four “upper‐case” alleles were at equal risk to be affected (and those with three or fewer were not at risk). Two of these loci were identical to marker loci, thus giving rise to weak disease‐marker associations. The other two were located between marker loci, with no linkage disequilibrium. Participants were given 200 nuclear families with at least one affected child, along with 100 control families with no affected individuals. The first two loci were intended to be detectable via association analysis. The remaining two loci were virtually undetectable in this data set. ©1995 Wiley‐Liss, Inc.