摘要:

AbstractVariation in the risk of insulin‐dependent diabetes mellitus (IDDM) across alleles at HLA‐A, B, and DR loci was investigated in a population‐based study of 801 families of children with newly diagnosed IDDM in Finland nationwide. Parallel analyses assessed the relative frequencies of alleles in IDDM children compared with age‐matched sibling controls and with the four possible genotypes which could have been inherited from the parents. The joint effects of DR3 and DR4 alleles were investigated under dominant, recessive, and additive models of gene expression. The additive model gave the best fit, though the relative risk for DR4 homozygotes was smaller than predicted. To investigate other alleles, we fitted the standard multiplicative model for alleles at each locus. After controlling for the correlation among alleles, significantly elevated risks were found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative risks between one and two. DR2 and DR5 were significantly negatively associated with IDDM, incurring less than half the risk. These findings support an independent role of class I antigens in the etiology of IDDM. © 1995 Wiley

ISSN:0741-0395    

DOI:10.1002/gepi.1370120502

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe fitted models for the main effects of alleles at the HLA‐A, B, and DR loci and their haplotypes on the risk of insulin‐dependent diabetes mellitus (IDDM). Empirical Bayes methods were used, assuming independent exchangeable normal priors for effects at each locus separately and for haplotype effects. A pure main effects model, pure haplotype effects model, and a combined model were fitted using Gibbs sampling. The main effects model showed that the DR locus had the largest variation in risk between alleles, followed by the B locus; significance tests for each allele in this model were in general agreement with those in the companion paper [Langholz et al. (1995)Genet Epidemiol12:441–453], although all relative risks were shrunk toward 1.0 in the empirical Bayes analysis. The variance estimate for pure haplotype effects was substantially larger than for any of the three main effects considered in this analysis, but in the combined model, the DR locus showed larger variability than the haplotype deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be common in Finnish diabetics does indeed confer unusually high risk (relative risk = 7.6,P<0.001), but found this to be only 1.9 times higher than predicted by its component main effects (P= 0.046). All of the other haplotypes could be adequately explained by their main effects. Empirical Bayes methods provide a natural means of dealing with the problems of multiple comparisons, multicolinearity, and sparse data that complicate the analysis of HLA data. ©1995 Wiley‐L

ISSN:0741-0395    

DOI:10.1002/gepi.1370120503

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

年代:1995

数据来源: WILEY

摘要:

AbstractRhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma whose cause is largely unknown. Reported risk factors include genetic alterations (e.g., p53 mutations, a defective gene at 11p15.5, or specific chromosomal translocation of t(2:13)), and parents' use of drugs around the time of conception. We present results from a national, case‐control study of 249 RMS cases (170 males and 79 females) and 302 controls (196 males and 106 females). The cases, aged 0–20 years at diagnosis, were identified via the Intergroup RMS Study‐III during 1982–1988. Controls were selected by random digit telephone dialing. As a supplement to the original study, information on genetic diseases and birth defects (BD) was collected from the subjects' parents by telephone interview. Fifty‐six (22.5%) cases and 55 (18.2%) controls were reported to have genetic diseases or BD (odds ratio [OR] = 1.30,95% confidence interval [CI]= 0.85–2.02,P= .21). The case group had a significantly higher frequency of neurofibromatosis type I (NF1) than did the control group, i.e., five cases (2.0%) had NF1 vs. zero controls (P= .02). The case group also had a higher frequency of major BDs than did the control group (6.0% vs. 2.6%, OR = 2.36, 95% CI = 0.92–6.52,P= .05). However, this excess was only observed in males (7.6% vs. 2.6%, OR = 3.16, 95% CI = 1.02–10.41,P= .02). Among the 15 cases having both RMS and major BDs, six (40.0%) had both conditions in the same regional anatomic site: Two (13.3%) had both in the extremities, two (13.3%) in the genitourinary system, and two in the head and neck. These findings suggest that common genetic mechanisms or in utero exposures may be invilved in the development of many childhood tumors and congenital abnormalities. ©1995

ISSN:0741-0395    

DOI:10.1002/gepi.1370120504

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

年代:1995

数据来源: WILEY

摘要:

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, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120505

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

年代:1995

数据来源: WILEY

摘要:

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, I

ISSN:0741-0395    

DOI:10.1002/gepi.1370120506

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe frequency of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene, detected byEcoRI andMspI, and their influence on serum lipids were studied in a total of 239 healthy subjects from the Belgrade area. The influence of interaction between different genotypes and smoking was also studied. The relative frequency of both rare R2 and M2 alleles (lacking the cutting site) was similar to that reported in other groups of Caucasians (0.16 and 0.11, respectively). No association was observed between the apo B genotypes and serum lipid levels adjusted for age, body mass index, and blood pressure either in the whole sample or in either women or men. When smokers and non‐smokers were considered separately, smoking had a significant impact on total cholesterol variability in all individuals with genotype M1M2 and high density lipoprotein (HDL) cholesterol variability in women with genotype R1R2. The presence of the rare alleles of these two polymorphisms in smokers was associated with lower lipid levels in the whole sample and in both women and men analyzed separately, except for an increase of HDL cholesterol level in male smokers, heterozygous forEcoRI polymorphism (R1R2). ©1995 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370120507

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

年代:1995

数据来源: WILEY

摘要:

AbstractFor a fully penetrant trait, apparent recombinants between the trait and marker loci result in an estimate of the recombination fraction θ>0. Given allowance for reduced penetrance and/or sporadic cases, this no longer need be true. In this short communication, we describe conditions under which θ is estimated to be zero despite the presence of apparent recombinants. We demonstrate that even if a large proportion of unaffected individuals are apparent recombinants and the penetrance is moderately high, the lod score may be maximized at θ = 0. Despite maximization at θ = 0, presence of apparent recombinants reduces the maximum lod score in comparison to its value if no apparent recombinants are present. ©1995 Wiley‐Lis

ISSN:0741-0395    

DOI:10.1002/gepi.1370120508

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn linkage analysis, estimated recombination fractions between a disease gene and several markers are used to assign the disease gene to a a particular chromosome region. For rare diseases, locus heterogeneity leads to different recombination fractions in different families, and a set of pedigrees can be regarded as a mixture. Information which can help to classify the different families may be available and can be included in the model. This is demonstrated for a data set of X‐linked retinitis pigmentosa families. The joint distribution of the position of the disease gene and the additional information on the penetrance of tapetal reflex among obligate female carriers is studied. A model including the additional information is fitted to the data using the EM algorithm. The algorithm uses for every pedigree the lod score curve which can be obtained from a standard (multipoint) linkage analysis. ©1995 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370120509

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

年代:1995

数据来源: WILEY

摘要:

AbstractPopulation studies of changes in human morbidity and mortality require models which take into account the influence of genetic and environmental factors on life‐related durations, such as age at onset of the disease or disability, age at death, etc. In this paper we show how a bivariate survival model based on the concept of correlated individual frailty can be used for the genetic analysis of durations. Six genetic models of frailty are considered and applied to Danish twin survival data. The results of statistical analysis allow us to conclude that at least 50% of variability in individual frailty is determined by environmental factors. The approach suggests a method of estimation of the lower bound for the biological limit of human longevity. Directions for further research are discussed. ©1995 Wiley‐Liss,

ISSN:0741-0395    

DOI:10.1002/gepi.1370120510

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.1370120511

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

年代:1995

数据来源: WILEY