摘要:

AbstractThis paper illustrates how epidemiologic principles can be used to investigate relationships between genetic susceptibility and other risk factors for disease. Five plausible models are described for relationships between genetic and environmental effects, and an example of a simple mendelian disorder that fits each model is given. Each model leads to a different set of predictions about disease risk in individuals with the genetic susceptibility alone, the risk factor alone, both, or neither. The risk predictions for the different models are described, and research designs for testing them are discussed.

ISSN:0741-0395    

DOI:10.1002/gepi.1370070302

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe familial resemblance of plasma apolipoprotein B (apo b) was investigated in a sample of 102 families including 419 members who volunteered for a free health checkup in the Preventive Center of Vandoeuvre‐lès‐Nancy, France. The mean levels (±SD) of apo B were 141.0 (±32.6), 121.8 (±27.7), and 98.6 (±22.6) mg/dl in fathers, mothers, and offspring, respectively. The familial correlations were 0.04, 0.13, 0.21 (P<.01), and 0.47 (P<.001) between spouses, father‐offspring, mother‐offspring, and siblings, respectively, after adjustment on age, body mass index, and sex. A genetic analysis was performed using the approach proposed by Bonney, which indicated that a recessive and a dominant major‐locus model appeared nearly equally supported by the data. Under the recessive model, the frequencyqof the most common allele was estimated as 0.825, with a mean difference of 60.4 mg/dl between high and low homozygotes. Under the dominant model,qwas estimated as 0.875, with a mean increase of 34.2 mg/dl in heterozygotes and high homozygotes. However, the hypothesis of Mendelian transmission and the environmental hypothesis could not be formally tested because of great numeric difficulties encountered in the estimation of the three transmission probabilities. Given these analytical restrictions, we cannot conclude in favor of a major locus influencing apo B level in our population, even though the evidence is suggestive. The genetic heterogeneity underlying the familial aggregation of apo B level, suggested by several recent publications, might explain the difficulty in discerning a single major locus in a population sample of small nuclear families, not ascertained through patients enriching the sample in high values of apo B. These findings call into question the relevance of the approach through “healthy” populations in the search for major loci influencing

ISSN:0741-0395    

DOI:10.1002/gepi.1370070303

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

年代:1990

数据来源: WILEY

摘要:

AbstractCirculating levels of low‐density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K. population. To investigate a possible genetic contribution to variation in LDL levels in differing populations we have extended this original study. RFLPs of the apo B gene were determined in samples of individuals from the United Kingdom, Finland, Italy, Spain, and Africa. Significant associations of LDL fractional catabolic rate with the apo B EcoRI and XbaI RFLP genotypes were detected only in the two North European populations. In the African population sample, the XbaI RFLP displayed a significant association with LDL apo B synthesis. The data suggest that variation in the apo B gene influences the metabolism of LDL and that it is different in individuals of different ethnic backgroun

ISSN:0741-0395    

DOI:10.1002/gepi.1370070304

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

年代:1990

数据来源: WILEY

摘要:

AbstractIn this study, we examined the relationship of two common genetic markers in black populations, sickle cell trait and glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency, to cardiovascular risk factors. The subjects were Nigerian civil servants in Benin City, Nigeria. We measured blood pressure, height, weight, sickle cell hemoglobin, G‐6‐PD, proteinuria, microalbuminuria and fasting serum cholesterol, high‐density lipoprotein cholesterol (HDL), triglycerides, apoprotein (APO) AI, and APO B. Data were collected on age, alcohol consumption, cigarette smoking, job status, and years lived in an urban area. There were 257 males (3 SS hemoglobin, 73 AS, 181 AA) and 69 females (23 AS, 46 AA). In comparing cardiovascular risk factors, males differed only in percent of smokers (31.5 in AS vs. 17.8 in AA,P<0.01). Among females, only high‐density lipoprotein (HDL) cholesterol differed (61.5 mg/dl in AS vs. 52.4 in AA,P<0.01). We hypothesize that females with sickle cell trait are more likely to use oral contraceptives than nontrait females. If so, the high‐estrogen oral contraceptives available in Nigeria could elevate HDL. G‐6‐PD deficiency status among males (52 deficient, 207 nondeficient) and females (1 deficient, 5 carriers, 65 nondeficient) was not related to any of the cardiovascular risk factors. We conclude that sickle cell hemoglobin trait and G‐6‐PD deficiency are not useful genetic markers for risk factors f

ISSN:0741-0395    

DOI:10.1002/gepi.1370070305

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

年代:1990

数据来源: WILEY

摘要:

AbstractWe have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to detect linkage has been examined by using the admixture test. We have varied the mode of transmission of each disease locus, the ascertainment of families and the proportion of cases in the population due to the linked disease locus. Generally, for the multiplex ascertainments we have considered, the power to detect linkage is greater when the linked disease locus has a high penetrance, when the unlinked disease locus has a low penetrance, and when pedigrees with multiple affected are selected. When selecting families with multiple affected, the rate of “mixed” families (i.e., those segregating for both disease loci) increases. However, for the pedigree structure we have considered, the power of the linkage test is more affected by a decrease in the rate of “linked” families than by an increase in the rate of “mixed” families. Finally, the present study shows that detection of linkage in presence of heterogeneity is feasible with a realistic sample size of small pedigrees as long as the linked disease locus accounts for more than 25% o

ISSN:0741-0395    

DOI:10.1002/gepi.1370070306

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

年代:1990

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370070307

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

年代:1990

数据来源: WILEY

ISSN:0741-0395    

DOI:10.1002/gepi.1370070301

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

年代:1990

数据来源: WILEY