摘要:

AbstractStandard methods of segregation analysis, such as originally developed in the unified model (UM) or the regressive logistic model (RLM) do not account for age of onset, and use instead age at examination. To take into account age of onset, models should be formulated using survival analysis concepts, as it was recently proposed with a model based on a logistic hazard function (LHM). A simulation study was conducted to compare the performances of the three methods (UM, RLM, and LHM) in analyzing generated familial data with variable age of onset. When the data were simulated under a polygenic hypothesis, all analysis models were robust with respect to the false conclusion of a major gene, if the tests of transmission probabilities were performed properly. When the data were generated under a major gene hypothesis, two main results were observed: (1) the use of the LHM markedly increased the power to detect a major gene, in particular when a genotype by age interaction was introduced in the model; and (2) in the situation of disease‐specific mortality, the use of either UM (whether specific mortality was accounted for or not) or RLM led to both spurious conclusions and bias in parameter estimates. These latter results obtained with the UM and the RLM can be explained by the violation of one constraint of both models observed in a situation of disease‐specific mortality, i.e., given all covariates, the probability of being affected and that of not being affected should sum to 1. The use of methods based on survival analysis concepts is recommended in the study of familial diseases with variable age of onset, especially in the case of a correlation between age of onset and age at examination which is induced by disease‐specific mortality. ©1995 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370120302

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

年代:1995

数据来源: WILEY

摘要:

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

ISSN:0741-0395    

DOI:10.1002/gepi.1370120303

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

年代:1995

数据来源: WILEY

摘要:

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 Epidemiol9:273–287 (1)]. Two examples based on published data sets are given to illustrate the proposed techniques. ©1995 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370120304

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

年代:1995

数据来源: WILEY

摘要:

AbstractOwing to the presence of outliers, an estimated 3.5% in the ridge breadth data and 1.7% in the height data, the effect of fragile X on height and ridge breadth was examined using robust statistical techniques for data collected from 54 families afflicted with this disorder. It is shown that fragile X affects ridge breadth and height in a different manner. Fragile X women had a greater mean ridge breadth than normal women, whereas there was a similar trend, but no significant difference, between normal and fragile X men. Fragile X men were shorter than normal men, but no significant difference between the mean height of normal and fragile X women was observed. However, fragile X girls were shown to grow more quickly and to stop growing earlier than normal girls. An examination of the covariance between relatives classified according to fragile X status showed that for both traits the effect of fragile X was to reduce the covariance between parents and offspring, which produced the effect of departure from an additive polygenic model of inheritance. ©1995 Wiley‐Liss, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120305

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

年代:1995

数据来源: WILEY

摘要:

AbstractA method is described for estimating excess relative risks of a disease from familial factors. Beginning with population‐based series of cases and controls, a cohort of each subject's relatives is formed and checked for disease against a population based registry. The disease experience of the cohort formed from each subject's relatives is summarized as a kinship‐weighted familial standardized incidence ratio (FSIR). The FSIR's are used as exposure estimates in conditional linear excess relative risk models, which may be used not only to screen for significant familial disease aggregations, but also to estimate relative risks, population attributable risks, and gene‐environment interactions. The method is demonstrated on 4083 breast cancer cases from Utah and a set of matched controls. ©1995 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370120306

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe human dopamine transporter gene, DAT1, acts to transport released dopamine into presynaptic terminals of the brain. The possibility that the DAT1 gene plays a role in genetic diseases of the brain has led to studies of DAT1 in several psychiatric and neurological disorders. Previous sequence analysis of DAT1 revealed a 40‐bp repeat in the 3′ end of the gene. In order to identify all potential alleles for this VNTR marker a population database was established. One thousand seventy‐four unrelated individuals were screened by PCR for the region containing the 40 bp repeat. Allele frequency differences were found between black Americans and Caucasians or Hispanics but no differences were observed between Caucasians and Hispanics. A previously unreported allele was detected in all three populations. Thus, we have shown that screening a large population identifies new alleles and generates more accurate allele frequencies. ©1995 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370120307

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe E*4 allele of the apolipoprotein E (APOE) gene on chromosome 19 has been shown to be an age‐ and dose‐related risk factor for Alzheimer's disease. Of 870 elderly women participating in an osteoporosis study, 13 were previously found to be homozygous for the APOE*4 allele; 1 was deceased and the rest were assessed for dementia in a “piggyback” study of dementia. One had moderate [clinical dementia rating (CDR) = 2], 2 had mild dementia (CDR = 1), and 2 had possible dementia (CDR = 0.5). All 3 women over 80 years were definitely demented (CDR ⩾ 1).Typically, genetic studies of Alzheimer's and other dementias require the identification and diagnosis of large numbers of demented subjects, at considerable expense, followed by genotyping or phenotyping with a relatively low yield of individuals with rare alleles. We demonstrate a more cost‐effective approach in which the population is first phenotyped and then stratified by phenotype, so that diagnostic evaluation can be restricted to individuals with the phenotype of interest. ©1995 Wil

ISSN:0741-0395    

DOI:10.1002/gepi.1370120308

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

年代:1995

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370120309

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

年代:1995

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370120310

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

年代:1995

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370120311

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

年代:1995

数据来源: WILEY