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R A Price

Publications and source records attributed to R A Price.

At least 73 records · Page 4Linked to original sources
PubMed1994

Obesity in Pima Indians: genetic segregation analyses of body mass index complicated by temporal increases in obesity.

During the past half-century the prevalence of obesity in developed countries has increased greatly. Such short-term changes in prevalence must be environmentally determined, but genes can mediate response to environmental change, for example, through variable gene penetrance and expression. Obesity differences between bith cohorts complicate the interpretation of phenotypic comparisons between generations that span periods of change. Genetic segregation analyses of the body mass index in 618 Pima Indian nuclear families (2 generations) identified recessive major gene inheritance, which is the same pattern of transmission that has been found in several other populations. However, within-birth-cohort analyses of siblings (one generation) uniformly supported codominant major gene inheritance with no polygenic heritability. For untransformed data transmission probabilities were Mendelian in the later-born cohort and in the combined sample of siblings. After transformation to remove skewness, transmission probabilities were Mendelian only in the earlier-born cohort (i.e., those siblings born before a period of marked temporal increase following World War II). A higher penetrance of codominant obesity susceptibility genes in the younger generation would result in some genetically obese individuals who have no affected parents, thus simulating recessive inheritance. Taken together, the results of these analyses suggest that the recessive pattern we identified in the Pima Indian nuclear families could be accounted for by temporal changes in penetrance of codominant obesity-predisposing genes. By implication, more modest temporal increases in white and black populations could in part account for the recessive pattern of inheritance described by several investigators.

Adolescent↗
PubMed1993

Obesity in Pima Indians: large increases among post-World War II birth cohorts.

Several studies have shown secular increases in obesity during the past 35 years, and others have reported increases in dietary fat consumption during the same period. Here we report a dramatic increase in obesity among Pima Indians born after World War II that appears to be associated with increased exposure to Western customs and diet following 1945. We examined the body mass index (BMI = weight in kilograms/height2 in meters) of 1,128 male and 1,372 female Pima Indians aged 15-65 years who were born between 1901 and 1964 and were examined between 1965 and 1990. We found large increases in BMI among Pima Indian men and women in post-World War II birth cohorts (1945 and later). The parallel changes in body mass index, dietary fat, and exposure to Western culture following World War II suggest that culturally mediated changes in diet and level of physical activity associated with modern industrialized society may have led to the large increases in obesity in the Pima Indians and to smaller parallel changes observed worldwide in westernized countries.

Acculturation↗
PubMed1993

Genetic segregation analysis of red blood cell (RBC) histamine N-methyltransferase (HNMT) activity.

Methylation is an important pathway in the biotransformation of many drugs, neurotransmitters, and xenobiotic compounds. Histamine N-methyltransferase (HNMT) catalyzes the N tau-methylation of histamine and structurally related compounds. Measurement of HNMT activity in the RBC makes it possible to access variation in the enzyme activity that may reflect differences in less accessible tissues such as brain. Previously reported high family correlations for RBC HNMT activity suggested that genetic inheritance plays a major role in the regulation of variation in this enzyme. In the present study we completed complex segregation analyses of RBC HNMT activity of 241 individuals in 51 nuclear families that were randomly ascertained through children in the Rochester, Minnesota public school system in order to characterize the mode of inheritance of this important enzyme. We found evidence for major gene influence on the regulation of RBC HNMT activity. Both transformed and untransformed data support the presence of Mendelian major gene segregation, but the gene frequency differences do not indicate a direct correspondence between genotypes inferred from the two sets of analyses. Analyses of the skewed untransformed data indicated the presence of a relatively rare (Q = 0.121) additive major gene for high activity, with the three overlapping genotype distributions representing 77, 21, and 2% of individuals. Analyses of the normalized transformed data indicated the presence of a common (Q = 0.71) additive major gene for high activity, with the three overlapping genotype distributions accounting for 9, 41, and 50% of individuals. The analyses of transformed data give the best fit as well as the most parsimonious Mendelian major gene model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Obesity in families of extremely obese women.

In order to assess the prevalence of obesity in families of extremely obese individuals, we conducted a mail survey of a national obesity organization. Thirty-nine percent (N=981) of the questionnaires were completed and returned. Respondents were excluded from further analysis if they were adopted, male, their gender could not be determined, provided incomplete information about their parents or their own height and weight, or were less than 22 or greater than 63 years of age. The analyses included 729 probands and their families. Both the prevalence and the extent of obesity were high in the families members. The average family members' body mass index (BMI=kg/m2) was 30, and 78% of the families studied had at least one other obese (BMI>30 kg/m2) first-degree relative (parent, sibling, or child). Although obesity was common in the families, survey respondents were generally the heaviest members of their families, having an average BMI of 47 kg/m2. Correlations among first-degree relatives were similar to those found for average weight groups, suggesting that obesity and BMI are similarly influenced by family genetic factors in this extremely obese population.

Adult↗
PubMed1993

A family history study of rapid-cycling bipolar disorder.

Previous studies have yielded mixed evidence as to whether rapid-cycling bipolar disorder (four or more episodes per year) is associated with a distinctive pattern of patient characteristics and familial aggregation of affective disorder. In this study, Family History Research Diagnostic Criteria (FH-RDC) were used to interview 165 patients with rapid-cycling bipolar disorder, non-rapid-cycling bipolar disorder, or recurrent unipolar depressive disorder about the psychiatric history of 812 adult first-degree relatives. In a validity study, FH-RDC diagnoses were demonstrated to agree reasonably well with best-estimate diagnoses by two psychiatrists/psychologists, based on direct interviews with the Structured Clinical Interview for DSM-III-R. Relatives of patients with recurrent unipolar depression were less likely to have bipolar disorder and more likely to have unipolar depression than were relatives of rapid-cycling or non-rapid-cycling bipolar patients. Rapid-cycling patients were younger and more likely to be female than non-rapid-cycling patients. The relatives of rapid cyclers did not differ significantly from those of non-rapid cyclers in the prevalence of bipolar disorder, unipolar disorder, rapid-cycling bipolar disorder, or substance abuse. However, there were nonsignificant trends for the relatives of rapid-cycling bipolar patients, compared with those of non-rapid-cycling bipolar patients, to have more substance abuse and less bipolar disorder given the presence of affective disorder.

Adult↗
PubMed1992

Extensive variation in evolutionary rate of rbcL gene sequences among seed plants.

Extensive variation in synonymous and nonsynonymous rates of substitution was observed among 50 sequences of the gene coding for the large subunit of ribulose-1,5-bisphosphate carboxylase (rbcL) representing bryophyte, conifer, dicot, and monocot taxa. Relative rate tests revealed rate differences of up to 138% for nonsynonymous substitutions and up to 85% for synonymous ones. Within angiosperms, the annual forms evolved more rapidly, on average, than perennial forms. This rate heterogeneity was more extensive at nonsynonymous sites than synonymous ones, and it resulted primarily from a recent acceleration of substitution rate in many groups of angiosperms.

Biological Evolution↗
PubMed1992

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.

Adolescent↗
PubMed1991

Changes in commingled body mass index distributions associated with secular trends in overweight among Danish young men.

The authors present results from a novel approach to understanding recent secular trends in overweight in terms of changes in underlying component distributions. On the basis of an examination of two large overlapping samples of Danish young men (ns = 16,557 and 21,747) spanning birth cohorts 1939-1958, the authors found evidence for two-component distributions, normal and overweight, in all cohorts. In cohorts born after 1940, the authors observed an increase in the size of the overweight component with no corresponding changes in overall mean or component means. On the basis of these results and other published reports, the authors speculate that the secular increase in overweight may be understood as a differential response to environmental change that may be mediated by genotype. The net effect appears to have been an increased penetrance in obesity-prone Danish young men.

Adult↗
PubMed1991

Inheritance of human plasma dopamine-beta-hydroxylase thermal stability.

Although the structural gene for human dopamine-beta-hydroxylase (DBH) has been cloned, the mechanism by which DBH physical properties and activity are regulated is not well understood. Previous reports have suggested that three-allele or two-locus models may account for the genetic regulation of these traits in human blood. It is an interesting challenge to determine the extent to which quantitative analyses will complement or guide molecular genetic studies. In this study we analyzed data on the physical property of DBH thermal stability and DBH activity in 230 individuals in 53 families in an attempt to clarify genetic mechanisms for the inheritance of these traits. Commingling and segregation analyses of the thermal stability data provided the first clear evidence of a major gene polymorphism for DBH thermal stability analyzed as a quantitative trait. Major gene transmission was supported within a mixed model (chi 2[3] = 13.39, P less than .004). In keeping with earlier findings, similar analyses of DBH activity provided strong evidence of genetic transmission. However, in our data support for a major gene polymorphism was equivocal (chi 2(2) = 2.99, P = .22).

Adolescent↗
PubMed1991

Body fat in identical twins reared apart: roles for genes and environment.

We report analyses of data on body fat from a cohort of 34 separated monozygotic twin pairs (MZA) and a matched sample of 38 pairs of monozygotic twins reared together (MZT) originally studied by James Shields. The correlation for MZA pairs was .61 and the correlation for MZT pairs was .75. These correlations did not differ significantly, nor did correlations differ between MZA pairs subclassified as having been raised in relatively more or less similar environments. Our results suggest important roles for both genes and environment in the accumulation of body fat and support other adoption studies in suggesting that adult environments rather than rearing environments are the most important nongenetic determinants of levels of body fat in adults.

Adipose Tissue↗
PubMed1991

Weight change in depression: influence of "disinhibition" is mediated by body mass and other variables.

The direction of weight change (gain or loss) in depression has recently been found to be a stable characteristic of patients across depressive episodes. A search for determinants of the direction of weight change revealed two candidates: the body mass index (BMI) (weight in kilograms/height in meters squared) and a psychological variable, "disinhibition" of dietary restraint. The present study, of 68 patients with a history of recurrent depression, found a significant correlation between BMI and weight change; in other words, heavier persons were more likely to gain weight if depressed. There was also a correlation between "disinhibition" and weight change. "Disinhibition" correlated with BMI and, when controlled for BMI, age and sex, the correlation between "disinhibition" and weight change fell to insignificance. We conclude that BMI along with age and sex mediated the correlation between "disinhibition" and weight change.

Appetite↗
PubMed1991

Inheritance of extreme overweight in black families.

We used complex segregation analysis to compare the genetic transmission of overweight in randomly selected black (N = 60) and white (N = 961) families. In both groups we found evidence for polygenic transmission. Major gene inheritance was strongly supported in whites and was marginally supported in blacks. Parameter estimates for black and white families were similar, suggesting that overweight is similarly transmitted in the black and white families we observed. There was evidence in both black and white families for high gene frequency and recessive gene expression. Extreme phenotypes common in black families may be the result of interactions between major genotype and polygenic or environmental factors; alternative explanations for differences in black and white families' transmission patterns are discussed. Replication with a larger group of black families is needed to confirm our findings.

Adolescent↗
PubMed1990

Common major gene inheritance of extreme overweight.

We studied 3925 individuals in 961 families to determine the mode of inheritance of overweight. As an index of overweight, we examined body mass index. Our analyses indicate that the most likely genetic model for susceptibility to overweight included moderate polygenic inheritance (34% of variance resulting from many genes with small effects) and common (21% frequency) recessively expressed major genes (a few genes with large effects on the individuals who possess them). Standard statistical criteria for accepting both polygenic and major gene inheritance were met, including tests of Mendelian transmission. These results suggest that recessive major gene inheritance of overweight may be common and that homozygosity for overweight susceptibility alleles often results in overweight. Clinical, biologic, and empirical observations all suggest genetic heterogeneity, that is, more than one predisposing gene.

Adult↗
PubMed1990

Childhood onset (age less than 10) obesity has high familial risk.

We assessed risk for obesity in 1743 first-degree relatives (parents and siblings) of 566 obese patients at three sites in the USA and one in Argentina. Onset of obesity prior to adulthood, and especially by age 10, significantly increased relative risk (2.14) for obesity in adult first-degree relatives. This increase in risk was consistent across four different patient samples from two different countries. Higher levels of obesity in patients were also associated with increased familial risk. Age of onset of obesity may be used to select obese adults with high genetic loading--an approach that should facilitate the identification of specific genes for human obesity. The enhanced ability to identify persons at high genetic risk for obesity provided by this study should increase the effectiveness of efforts to prevent obesity.

Adolescent↗
PubMed1990

Secular trends in body mass index among Danish young men.

Body mass index (weight/height 2; kg/m2) of 38,132 Danish young men, representing approximately 10 percent of those undergoing mandatory draft board examination was analyzed with regard to secular changes through the birth cohorts 1939-58 in the Greater Copenhagen area and a western provincial region, and through the cohorts 1947-58 in two other provincial areas. The 25th, 50th, and 75th percentiles of body mass index remained essentially unchanged over time. The prevalence of obesity (body mass index greater than or equal to 30 kg/m2) showed a steep increase in birth cohorts beginning in the early 1940s and a levelling off thereafter. The secular increase in prevalence of obesity without similar trends in median body mass index strongly suggest the existence of environmental causes of obesity to which the study population was increasingly exposed. The changes may have occurred either in specific causes of obesity or, most likely, in more general environmental conditions causing obesity only together with genetic predisposition, for which there is growing evidence.

Adolescent↗