摘要:

AbstractA major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 ± 2.5, 141.9 ± 4.4, and 208.1 ± 11.5 for low homozygotes, heterozygotes, and high homozygotes, respectively. The corresponding genotypic frequencies were 0.718, 0.259, and 0.023. the apoB locus explained 13% and 14% of the variance in total and low‐density‐lipoprotein cholesterol levels, respectively. Persons with elevated apoB had normal to high levels of total serum cholesterol and triglyceride and low to normal levels of high‐density lipoprotein and apolipoprotein A‐I. Sixteen members of three of the pedigrees were heterozygous for familial hypercholesterolemia (FH). Their apoB levels were estimated as 35.72 ± 7.16 mg/dl above the apoB genotypic means, assuming that the two loci act independently. Therefore, two major loci, the FH locus and the apoB locus, affect two levels, apoB and LDL

ISSN:0741-0395    

DOI:10.1002/gepi.1370040202

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

年代:1987

数据来源: WILEY

摘要:

AbstractTwo French Canadian families among whom the Tay‐Sachs allele is segregating are analyzed to investigate whether there is residual phenotypic familial covariation over and above that from major gene segregation. The traits analyzed are functions of hexosaminidase A (HEXA) and hexosaminidase B (HEXB) levels, and a combination of segregation and discriminant analysis is used to find a function of HEXA and HEXB levels to discriminate between carriers and noncarriers in this French Canadian population. We found that residual familial covariation is significant for the ratio HEXA/(HEXA + HEXB), the statistic generally used to determine if an individual is likely to be a carrier of the Tay‐Sachs allele in Ashkenazi Jewish populations. This suggests that the ratio may not be appropriate for the French Canadian group and that the mutation may be different from that in Ashkenazi Jews. A linear function is calculated that gives improved discrimination between carriers and noncarriers for the two French Canadian pedigrees stud

ISSN:0741-0395    

DOI:10.1002/gepi.1370040203

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

年代:1987

数据来源: WILEY

摘要:

AbstractWhen a multivariate normal sample is chosen from a truncated space of one of its components one can no longer make use of the normality assumption for the sample observations or for the estimates derived from them. In this paper, skewness and kurtosis for each component are derived analytically under a broad class of nonrandom sampling. It is shown that the distortions in skewness and kurtosis produced by nonrandomness are negligible, except those for the component with respect to which the selection of sampling regions is based. The ususal tests of normality from sample values of skewness and kurtosis measures remain valid under nonrandom sampling, except for the selection variable. The implications of these analytical results in the context of commingling analysis in genetic epidemiology are discussed. It is recommended that when samples of families are obtained through nonrandomly ascertained probands, a commingling analysis should treat each relative class separately, since such analyses based on the pooled sample of individuals may involve unspecified bias in the levels of the test procedure.

ISSN:0741-0395    

DOI:10.1002/gepi.1370040204

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

年代:1987

数据来源: WILEY

摘要:

AbstractA study of gastric pH, nitrate, and nitrite in 110 families collected as part of a cohort from the Narino region of Colombia is presented. All three traits are familial and have a significant linearly increasing age trend. Gastric pH has a clear bimodal distribution but does not show Mendelian segregation. The nitrate distribution is slightly skewed, but generational heterogeneity explains the data best. Gastric nitrite is also biomodal with a clear break at concentration 1.08 μg/ml, and 74% of the observations at zero concentration; it shows a recessive Mendelian segregation with significant residual spouse correlation. This model also fits the data best when nitrite is dichotomized into detected (measurable) and undetected values. The estimated frequency of the recessive allele is .57, so that an estimated 32% of the population sampled are recessives. Recessives whose spouses have measuarable nitrite have an estimated penetrance of 99.3% at age 30 years, whereas those whose spouses have zero or undetected nitrite have a penetrance of only 8.8% at age 30 years. It appears that gastric nitrite, and, from our previous study of these families, chronic atrophic gastritis are important biologic markers for the early identification of persons predisposed to gastric cancer

ISSN:0741-0395    

DOI:10.1002/gepi.1370040205

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

年代:1987

数据来源: WILEY

摘要:

AbstractRobust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait‐marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL‐C levels, the HDL‐C to apo A1 ratio, the LDL‐C to apo B ratio, and a measure of relative content of cholesterol in HDL‐C and LDL‐C. Linkage between haptoglobin and the HDL‐C/apo A1 ratio was suggested, with a lod score of 1.7

ISSN:0741-0395    

DOI:10.1002/gepi.1370040206

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

年代:1987

数据来源: WILEY

摘要:

AbstractResults of a Monte Carlo study to investigate the properties of three statistical methods used extensively in path analysis of family data are presented. All three methods are based on the maximum likelihood principle and involve the assumptions of multivariate normality and large sample (asymptotic) statistical properties. The methods differ, however, in the specification of the likelihood function. Given a set of correlation estimates, method 1 maximizes the likelihood function under the stipulation that the estimates are independent. Method 2 differs from the former by allowing for covariances among the correlation estimators. Method 3 involves (direct) maximization of the likelihood function for the individual family observations assuming multivariate normality for the vector of family observations. The Monte Carlo study investigated validity of the test statistics and confidence intervals and evaluated the relative efficiency and bias of the parameter estimates based on 1,000 replications of each of several simulation conditions. The effects of violating the two basic assumptions, multivariate normality and asymptotic theory, were investigated by comparing results for non‐normally vs normally distributed family data and for small vs large sample sizes. It is shown that method 3 provides valid statistical inferences under multivariate normality and that it is generally robust against minor departures from normality. Method 2 is also robust against minor deviations from normality, but it is sensitive to small sample sizes. Method 1 yields highly conservative test statistics under all conditions studie

ISSN:0741-0395    

DOI:10.1002/gepi.1370040207

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

年代:1987

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370040208

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

年代:1987

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370040209

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

年代:1987

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370040210

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

年代:1987

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370040201

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

年代:1987

数据来源: WILEY