ABSTRACT
A path analytic model for the analysis of nuclear family data is described and used to analyze the results of two major studies of cholesterol (CH) and triglyceride (TG), the Honolulu Heart Study (HHS) of Japanese-Americans and the Cincinnati Lipid Research Clinic (LRC) study of Caucasians. The studies were first analyzed separately to assess evidence for genetic and cultural transmission, marital resemblance, and maternal environmental effects for the two plasma lipids, and then simultaneously to identify the nature and sources of any between-study-heterogeneity. There were significant sources of heterogeneity between the two studies for CH (only marital environmental resemblance and non-transmitted sibling environmental resemblance) and for TG (only non-transmitted sibling environmental resemblance). The two studies were homogeneous with respect to the magnitude of genetic and cultural effects; for CH genetic heritability was estimated as h2 = .594 +/- .041 while cultural heritability was estimated as c2 = .035 +/- .008, and for TG the two heritabilities were estimated as h2 = .259 +/- .034 and c2 = .108 +/- .014. An additional bivariate analysis of the association between the two lipids revealed that all phenotypic resemblance could be explained in terms of an association of non-transmitted residual environments with little evidence for a genetic association. The relevance of these results for an understanding of the genetic epidemiology of plasma lipids is discussed.
Subject(s)
Cholesterol/genetics , Triglycerides/genetics , Asian People , Child , Cholesterol/blood , Cultural Characteristics , Hawaii , Humans , Japan/ethnology , Mathematics , Models, Genetic , Phenotype , Triglycerides/blood , White PeopleABSTRACT
The pattern of inheritance of fasting blood glucose was examined in a Japanese cohort of 500 nuclear families living in Hawaii. A principal component of glucose was defined to improve the ranking of diabetics and individuals receiving treatment (medication and/or diet) for hyperglycemia, thereby allowing as well as possible for inability to determine untreated levels in patients. Results from path and segregation analysis show that family resemblance for glucose is low in this population. The additive variation can be explained by a cultural model of inheritance without introducing intergenerational differences, a maternal-paternal effect, or even genetic parameters. Heritability is approximately 0.125. Complex segregation analysis provides no convincing evidence for a major gene, with preliminary support based upon leptokurtic outliers in five families disappearing on further analysis by partial truncation. A claim by other workers of a major recessive gene for hyperglycemia may be due to their failure to allow for treatment, skewness, and multifactorial heritability. In future, the search for major loci acting on liability to hyperglycemia should use multiple determinations of fasting glucose or be addressed to more primary and repeatable variables than fasting blood glucose.
Subject(s)
Blood Glucose/genetics , Diabetes Mellitus/genetics , Adult , Child , Female , Hawaii , Humans , Japan/ethnology , Male , Models, Genetic , Statistics as TopicABSTRACT
Blood pressure gave evidence for genetic heritability (0.24 for systolic 0.19 for diastolic) and for cultural heritability (0.16 for systolic, 0.09 for diastolic in children) in a sample of Japanese-American families. A small but significant fraction of cultural inheritance was due to maternal effects, possibly mediated through dietary habits. There was no convincing evidence for major loci causing hypertension in this population, and the polymorphism proposed by Platt was excluded as a principal cause of hypertension.
Subject(s)
Blood Pressure , Ethnicity , Adult , Chromosome Mapping , Cultural Characteristics , Diet , Extrachromosomal Inheritance , Female , Hawaii , Humans , Hypertension/genetics , Japan/ethnology , Male , Middle Aged , Phenotype , Polymorphism, GeneticABSTRACT
Obesity, alcohol consumption, and hematocrit provide an index of plasma uric acid, which in path analysis has a cultural heritability of 0.11 in children and 0.23 in parents, a small maternal effect, and a genetic heritability of 0.25 in both generations. Preliminary evidence for a major locus is destroyed by the omission of one exceptional child. There is no evidence against the polygenic hypothesis for hyperuricemia in the Japanese-American population studied.
Subject(s)
Genetic Variation , Uric Acid/blood , Adult , Alcohol Drinking , Female , Hematocrit , Humans , Male , Middle Aged , Obesity/physiopathology , Phenotype , Sex FactorsABSTRACT
A general linear model is presented here for biological and cultural inheritance involving ten parameters to be estimated from 16 correlations in nuclear families, providing ample degrees of freedom to test goodness of fit. Applied to six lipoprotein traits the model fits acceptably to all, although there is evidence of transient maternal effects for cholesterol and lipemia. Genetic heritability in children ranges from 0.175 for triglyceride to 0.562 for total cholesterol. Cultural heritability in children ranges from 0.012 for VLDL to 0.149 for HDL-cholesterol.
Subject(s)
Lipoproteins/genetics , Adult , Age Factors , Child , Culture , Environment , Female , Genotype , Humans , Lipoproteins/blood , Male , Models, Biological , Nuclear Family , Phenotype , Sex FactorsABSTRACT
In more than 500 families of Japanese ancestry, selected in part through fathers with hyperlipemia or coronary heart disease, a major locus for hyper-beta-cholesterolemia (hyperlipoproteinemia type IIa) is highly significant (chi22 = 24.02), with an allele frequency .002 in the general population. This gene is revealed with about the same power by fasting levels of LDL (low density lipoprotein) cholesterol and total cholesterol. However, VLDL (very low density lipoprotein) cholesterol, HDL (high density lipoprotein) cholesterol, and triglyceride give no convincing evidence for a major locus in this population, nor was a gene for combined hyperlipoproteinemia detected.
Subject(s)
Gene Frequency , Lipoproteins/blood , Female , Humans , Hypercholesterolemia/genetics , Male , Mathematics , PhenotypeABSTRACT
A "sinking" pre-beta lipoprotein was sought in a probability sample of 1854, 50--72-year-old men of Japanese ancestry in Honolulu by ultracentrifugation of plasma and electrophoresis of the bottom fraction (density greater than 1.006) in agarose. A definite electrophoretic band was found in 5.6% of the men and a trace band was found in 4.6% of them. The frequency of such a band increased with age and decreased with adiposity. The relative risk for coronary heart disease, based on prevalence cases was found to be 1.7 in men with a definite band, and 1.4 in those with a trace band, when compared to men without. This association could not be explained by the higher low density lipoprotein levels in men with trace or definite bands. These data are consistent with previous reports suggesting that the Lp antigen (for which a sinking pre-beta lipoprotein is probably an insensitive marker) is associated with coronary disease.
Subject(s)
Coronary Disease/blood , Lipoproteins, VLDL/blood , Age Factors , Aged , Cholesterol/blood , Hawaii , Humans , Japan/ethnology , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Male , Middle Aged , Obesity/blood , Risk , Sampling StudiesABSTRACT
The Lp gene frequency is estimated to be 0.083 in Japanese, but with our method of assay the evidence favoring a major locus is marginal. The sinking pre-beta band is significantly associated with elevated cholesterol and depressed triglyceride. The biological significance of these observations is discussed.
Subject(s)
Gene Frequency , Lipoproteins/genetics , Cholesterol/genetics , Female , Humans , Japan , Male , Triglycerides/geneticsABSTRACT
In a sample of nearly 8,000 Japanese males, the distributions of casual cholesterol and triglyceride, hematocrit, glucose, uric acid, diastolic blood pressure, and weight (covariance adjusted) could not be normalized by a power transform and were significantly better fitted by a mixture of distributions. The evidence for admixture was nonsignificant for systolic blood pressure, significant but unimpressive for height and weight, and strong for the remaining variables. The minor component corresponded to high values, in low frequency except for triglyceride and glucose. These results favor an interpretation of elevated levels in terms of distinct entities, genetic or environmental or both, rather than cumulative small effects only. These entities appear to be megaphenic (i.e., with effects exceeding one phenotypic standard deviation). Consequences of this hypothesis are discussed.
Subject(s)
Genetics, Medical , Genetics, Population , Statistics as Topic , Aged , Blood Glucose , Blood Pressure , Body Height , Body Weight , Cholesterol/blood , Hematocrit , Humans , Male , Middle Aged , Triglycerides/blood , Uric Acid/bloodSubject(s)
Alcohol Drinking , Lipoproteins/blood , Obesity/blood , Smoking , Age Factors , Hawaii , Hematocrit , Humans , Japan/ethnology , Male , Sex Factors , Smoking/complicationsABSTRACT
To ascertain the frequency of defined hyperlipoproteinemia and to investigate the relation between lipoprotein fractions and coronary heart disease, we measured serum lipoprotein cholesterol levels in a population-based sample of Hawaii Japanese men 50 to 72 years old. Type II hyperlipoproteinemia was present in 3 per cent of 1859 men, and Type IV in 26 per cent. Relative risks for coronary heart disease, based on 264 prevalence cases, were found to be 1.8, 1.8 and 0.46, between the upper and lower quartiles of total, beta, and alpha cholesterol, respectively. We found no significant relation between triglyceride and coronary heart disease. The inverse relation of alpha cholesterol of prevalence of coronary heart disease was independent of beta cholesterol, obesity, and other factors. The data suggest the need for further evaluation of the protective effect of the alpha lipoprotein fraction on the development of coronary heart disease.
