摘要:

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.

ISSN:0741-0395    

DOI:10.1002/gepi.1370110202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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.

ISSN:0741-0395    

DOI:10.1002/gepi.1370110203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370110204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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. ©

ISSN:0741-0395    

DOI:10.1002/gepi.1370110205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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,

ISSN:0741-0395    

DOI:10.1002/gepi.1370110206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractMethods are proposed for the analysis of diseases with variable age at onset. The Cox proportional hazards model, widely used for epidemiologic analysis, is modified to include both measured (environmental) covariates and latent (genetic) variables, as well as their interactions. A Monte Carlo technique known as Gibbs sampling is utilized to generate observations from the posterior distributions of all model parameters. A correction to account for single ascertainment of pedigrees is also described. Simulation studies show that parameter estimation is nearly unbiased for a wide variety of models, and that moderate gene‐environment interaction effects can be detected. © 1994 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370110207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

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 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370110208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe weighted rank pairwise correlation (WRPC) statistic has been proposed as a robust test of genetic linkage, particularly adapted to the analysis of large and complex pedigrees and for age‐dependent and heterogeneous diseases. In this paper a simulation study is presented. Validity and power of the WRPC test are studied and compared to the Haseman‐Elston sibpair method for various types of problems. The power of the WRPC test is slightly lower than the Haseman‐Elston method for analyzing a large number of small randomly chosen pedigrees. It is higher however in presence of genetic heterogeneity or for analyzing large individual pedigrees. Recently, evidence of linkage of Alzheimer's disease with a locus on chromosome 14, D14s43, has been obtained by the Lod‐score method. We reanalyze these data using the WRPC test, essentially confirming the results of the Lod‐score method. The WRPC test statistic is higher than the equivalent Lod‐score statistic for the two pedigrees which show strong evidence of linkage with the two methods. The global WRPC test statistic is slightly lower than the Lod‐score test statistic. The WRPC test, however, makes no hypothesis of a specific genetic transmission model and can be computed very quickly; in addition, an exactP‐value can be computed by simulation for individual pedigrees. © 1994

ISSN:0741-0395    

DOI:10.1002/gepi.1370110209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370110201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY