摘要:

AbstractFor all patients with multiple sclerosis in Orkney who were alive in 1974 or who had died during 1958 to 1974, pedigree data were analysed. The relationship between their parents, expressed by kinship coefficients, was compared with that between parents of matched controls. The closer relationship between parents of patients suggests that it is the genes that are shared by a patient's parents, and that he inherits from both, that influence his susceptibility to multiple sclerosis.

ISSN:0741-0395    

DOI:10.1002/gepi.1370080302

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe examined the mode of inheritance of rheumatoid arthritis (RA) and estimated the genetic contribution of the HLA‐linked locus to the development of RA using data from 111 multiplex families (54 London, 57 Cleveland), and 43 randomly ascertained patients (Seattle). HLA‐DR4 was present in 78 multiplex probands (70%); a further 16 probands who were negative for DR4 were positive for DR1. Both DR4 and DR1 were significantly in excess when compared to control population frequencies (P<0.001); an additional finding was an excess of DR7, although the numbers of probands with DR7 were small. Despite the well‐established HLA association with RA, neither recessive nor additive (dominant) modes of inheritance, nor any intermediate models have been ruled out using affected sib‐pair and antigen genotype frequency among patients (AGFAP) methods. However, in our study the AGFAP data for HLA‐DR4 and DR1 were close to recessive expectations (P= ns) while an additive (dominant) mode of inheritance was rejected (P<0.001). The same results were obtained by an independent method which considered HLA‐DR transmission from affected parents to their affected children. The affected sib‐pair haplotype sharing method showed deviation from random expectations but did not allow discrimination between recessive and additive (dominant) modes. The effect of the HLA‐linked locus on familiarity accounted for only a 1.61‐fold increased risk to sibs over the population prevalence, compared to an observed value of 3.90. This indicated that there could be at least one other non‐HLA locus predisposing to RA with a weight that is slightly great

ISSN:0741-0395    

DOI:10.1002/gepi.1370080303

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

年代:1991

数据来源: WILEY

摘要:

AbstractChildren of fathers with insulin‐dependent diabetes mellitus (IDDM) are at greater risk of developing the disease than are children of IDDM mothers, reasons for which are currently unknown. To explore the possibility that genomic imprinting contributes to this phenomenon, 1,774 families with at least one IDDM child diagnosed before the age of 17 years and between 1950 and 1981 from the Children's Hospital at Pittsburgh IDDM Registry were evaluated. Approximately 1% of the mothers and 2.9% of the fathers were reported to have IDDM diagnosed before the age of 36 years (P0.05). These data are not consistent with the genomic imprinting hypothesis and suggest that other genetic and/or environmental factors contribute to the increased risk for children of IDDM father

ISSN:0741-0395    

DOI:10.1002/gepi.1370080304

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

年代:1991

数据来源: WILEY

摘要:

AbstractAs part of our ongoing studies of genetic markers of reproductive outcome in the Hutterites, we have been analyzing potential risk factors for pregnancy outcomes. In particular, we are interested in the effects of HLA sharing between parents on fetal loss rates. Pregnancy outcome data such as these have two characteristics that create statistical challenges, i.e., repeated observations per couple and between‐couple heterogeneity in risk. We critically examine four approaches based on the logistic model for the analysis of this and similar data: 1) unconditional likelihood analysis with and without fixed cluster effects; 2) conditional likelihood analysis; 3) mixed‐effects analysis with random cluster effects; and 4) the robust generalized estimating equation (GEE) procedure. Of these approaches, the GEE method of Liang and Zeger would be best suited for the analysis of our data when the question of interest concerns a variable that is constant over all pregnancies, such as HLA sharing. If the question concerns a couple's risk associated with a changing variable such as maternal age, the mixed‐effects analysis is the more approp

ISSN:0741-0395    

DOI:10.1002/gepi.1370080305

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

年代:1991

数据来源: WILEY

摘要:

AbstractA number of studies have documented the familial aggregation of lung cancer; there is at least one report that female reproductive cancers are also increased in these families. To determine if the risk exists for all reproductive cancer sites, we conducted a nested case‐control study of lung cancer incidence in a cohort of 41,837 women ages 55–69 years. Women were recruited by mail and asked to provide information on education, occupation, smoking habits, physical activity, and family history of specific cancer sites among female relatives. Four year follow‐up for cancer incidence was conducted using a state‐wide tumor registry. Compared to random controls (n= 1900), cases (n= 152) were more likely to have reported at baseline a sister affected with cancer of the uterus [crude odds ratio (OR) = 3.4, 95% Cl = 1.7–7.0,P<0.01], cervix (OR = 3.2, 95% Cl 1.2–8.6,P<0.05), or cancer at any site (OR = 1.6, 95% Cl 1.1–2.4,P<0.05). A family history of an affected mother with a female reproductive cancer was also more common among the cases, but not statistically significant. Cases were less educated, more likely to work in a technical/industrial setting, less physically active, more likely to smoke, and to smoke for a longer period of time than the controls (allP<0.01). These differences reduced the magnitude of the family history risk indicators; only the combined category of reproductive cancer at all sites among sisters remained statistically significant. Additional family studies should be done to assess environmental factors in the relatives of the cases and controls to disentangle the influence of shared genes and shared environmental factors in these

ISSN:0741-0395    

DOI:10.1002/gepi.1370080306

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

年代:1991

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370080301

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

年代:1991

数据来源: WILEY