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PubMed1985

Familial analysis of qualitative traits under multifactorial inheritance.

The analysis of family data is described for qualitative multifactorial traits. For such a trait, affectational status is determined by an underlying liability distribution with one or more thresholds. The distribution of families (either selected at random or through probands) is used to estimate sex-specific parent-offspring and sibling correlations in liability and the prevalence in each sex. In contrast to using pairs of relatives, this approach permits estimation of age-specific population prevalences without a control sample. Moreover, by allowing for sex-specific correlations and a correlation between mates, path analysis can be used to model and test various cultural transmission models in addition to polygenic inheritance. Parameter estimation, hypothesis testing, and a goodness-of-fit test for path analytic models are described, and a computer program implementing these procedures is outlined.

Age Factors↗
PubMed2005

Rare variant hypothesis for multifactorial inheritance: susceptibility to colorectal adenomas as a model.

The rare variant hypothesis postulates that genetic susceptibility to colorectal neoplasia within the general population is due to a number of low frequency variants in a variety of different genes. Each variant confers a moderate, but detectable, increase in relative risk of developing the disease. Recent evidence suggests that a quarter of patients with multiple adenomatous polyps are due to rare but functionally important variants in just five genes.

Adenoma↗
PubMedDate not supplied

[Genetic influence on energy requirements. III. Multifactorial inheritance modified by gender].

A conversion index (CI) which measures the efficiency of utilization of dietary energy was found to be normally distributed in Wistar rats. The CI used was a ratio of the amount of food ingested to achieve an increment of one gram of body weight during the period of 32 days starting on day 21 after weaning. We have previously reported that male rats are more efficient energy converters than females. As a way to explore the hypothesis that the inheritance of the regulation of energy requirements is multifactorial, we mated F1 rats with high CI (poor energy converters) and studied the CI of their F2 offspring. The males behaved in agreement with the hypothesis as the F2 males had higher CI than the F1 males, but the behavior in females was different, i.e. the F2 were better converters than the F1. We have no explanation for this gender discrepancy.

Animals↗
PubMed1995

Utilization of dietary energy in the rat. IV. Multifactorial inheritance modulated by gender.

In Wistar rats the conversion indexes (CIs) are normally distributed. A conversion index is the amount of food consumed necessary to increase the body weight by 1 g in a 32-day period, which begins at weaning (day 21) and ends on the 52nd day of life of the rat. Some experiments have been designed trying to demonstrate that inheritance of energy dietary utilization in Wistar rats may be multifactorial modulated by gender. In the study presented here parental males (F1) with CIs below the male median were paired with females of the same F1 who also had CIs below the female median. It was postulated, if the hypothesis is correct, that the offspring (F2) obtained from these pairings would have conversion indexes below the median of the CIs of the parental rats(F1). The results indicate precisely that both males and females behave as expected. Thus it appears that inheritance of efficiency of dietary energy utilization in the Wistar rat is a multifactorial trait.

Animals↗
PubMed1989

Multifactorial inheritance and recurrence risks of multiple sclerosis in Italian patients.

This study is based on 166 patients with definite multiple sclerosis (MS) residing in different Italian regions and on 332 parents and 326 siblings. Seven patients had a first-degree relative with a definite diagnosis. The comparison with a population age-matched for specific frequency of MS showed an increase of the disease among relatives. The increase in MS frequency among sibs is compared with that expected under an autosomal dominant, autosomal recessive or multifactorial model. The multifactorial hypothesis appears to better fit the data. The heritability index is calculated for each combination of relative and affected patient sex and compared with estimates of other European and American countries. The recurrence risk rates for male and female relatives have been computed for the more frequent family situations. Our results support the hypothesis of a multifactorial model of inheritance and provide risk figures to be used in genetic counseling.

Adult↗
PubMed1979

Multifactorial inheritance with cultural transmission and assortative mating. III. Family structure and the analysis of separation experiments.

Demographic data about family composition or structure in the United States is reviewed. About 25% of white children and a majority of black children are reared in either broken or extended families, and this must be taken into consideration for valid studies of cultural inheritance. Atypical family structures are described including those in which parents include: biological parents, stepparents, grandparents, uncles, aunts, sibs, foster parents, and their spouses. General formulae for a wide variety of kinship correlations are derived using path analysis. The multifactorial model presented allows for cultural inheritance, polygenic inheritance, correlated sibling environments, and phenotypic assortative mating (as previously described for intact families) plus extensions necessary for the analysis of separation experiments. These extensions allow for variable family structure and differences in parental influence due to separation, age or stage of development of the child, birth order, or type of relationship. Family structure is observed to have a marked effect on familial resemblance. Computer simulation studies demonstrate marked heterogeneity among phenotypic correlations for kinships of the same degree of genetic relationship arising in different family structures. Analyses of multiple types of sibs and other relatives in variable family structures offer great promise for the study of cultural inheritance.

Adolescent↗
PubMed1996

Multifactorial inheritance of non-syndromic macrocephaly.

OBJECTIVE: To reevaluate previous claims that non-syndromic macrocephaly is usually inherited as an autosomal dominant trait. DESIGN: Head size was measured in the parents and sibs of children with non-syndromic macrocephaly. OUTCOME MEASURES: If autosomal dominant inheritance is involved, the frequency distribution should be bimodal. RESULTS: Head circumference of parents and sibs of the macrocephalic probands had a mean significantly greater than the population norm, and a unimodal distribution. Probands with psychomotor impairment had bigger heads, and more had a history of birth difficulty, than did unimpaired probands. CONCLUSIONS: The usual genetic basis for non-syndromic macrocephaly is multifactorial with a polygenic genetic basis, rather than autosomal dominant. Risk of recurrence appears to be much lower than if it would be on the assumption of autosomal dominant inheritance. Macrocephaly in a parent or sib of an unborn child may present a risk for birth injury to that child. A larger series of patients will be necessary to resolve this question.

Adult↗
PubMed1995

Multifactorial inheritance in type 1 diabetes.

To date, twelve separate chromosome regions have been implicated in the development of human type 1 (insulin-dependent) diabetes mellitus. The major disease locus, IDDM1 in the major histocompatibility complex(MHC) on chromosome 6p21, accounts for about 35% of the observed familial clustering and its contribution to disease susceptibility is likely to involve polymorphic residues of class II molecules in T-cell-mediated autoimmunity. IDDM2 is encoded by a minisatellite locus embedded in the 5' regulatory region of the insulin gene. Familial clustering of disease can be explained by the sharing of alleles of at least 10 loci. IDDM1 and IDDM2 interact epistatically. For a multifactorial disease, such as type 1 diabetes, important information concerning the pathways and mechanisms involved can be gained from examining such interactions between loci, using methods that simultaneously take account of the joint effects of the various underlying genetic components.

Animals↗
PubMed1986

Heterogeneity in multifactorial inheritance of plasma lipids and lipoproteins in ethnically diverse families in Jerusalem.

Genetic and cultural determinants of total cholesterol (TC), triglyceride (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and HDL-C/TC were estimated utilizing a path model in a random sample of nearly 4,000 families examined in the Jerusalem Lipid Research Clinic. The analyses were done separately in each of the ethnic groups categorized according to the parents' country of birth (Europe, Asia, North Africa, and Israel/mixed origin) in order to identify the nature and sources of any heterogeneity among the groups. Both genetic (h2) and cultural (c2) components of inheritance were significant for all lipid variables in each of the ethnic groups. Under the most parsimonious model, estimates of h2 in the ethnic groups were .40-.55, .40-.51, .45-.50, .41-.48, and .42-.78 for TC, LDL-C, HDL-C, HDL-C/TC, and TG, respectively. The c2 ranged from 3% to 5% for TC and LDL-C and from 4% to 10% for HDL-C, HDL-C/TC, and TG. The major parameters of the path model were generally homogeneous across the origin groups. The h2 appeared to be higher in the Asian and c2 was slightly greater in the European group. The stronger sibling environmental effect in the Asia group, the somewhat lower transmission of environment in the North African group, and the lower correlation between spouse environments in the North African group were the major sources of the origin heterogeneity. Within this population, genetic factors appear to be the major determinants of lipid variations, suggesting relative homogeneity of the distribution of environmental determinants of plasma lipids.

Adolescent↗