Biomedical subjects

M N Chiano

Publications and source records attributed to M N Chiano.

7 recordsLinked to original sources

PubMed1999

Genetic and environmental influences on total-body and central abdominal fat: the effect of physical activity in female twins.

BACKGROUND: The increasing prevalence of obesity has focused attention on the contribution of physical activity and its interaction with predisposing genetic factors. OBJECTIVE: To examine 1) the relation between physical activity and total-body and central abdominal fat, independent of genetic and other environmental factors, and 2) the influence of physical activity in persons who are genetically susceptible to generalized or central adiposity. DESIGN: Cross-sectional study. SETTING: A London academic teaching hospital. PATIENTS: 970 healthy female twins (mean age, 55.5 years [range, 39 to 70 years]; body mass index, 24.4 kg/m2 [range, 16.4 to 44.0 kg/mg2]). There were 241 monozygotic pairs, 228 dizygotic pairs, and 32 women whose co-twin lacked complete data. Fifty-six percent of participants were of normal weight, 30% were overweight, 7% were obese, and 7% were underweight. MEASUREMENTS: Total-body and central abdominal fat were measured by dual-energy x-ray absorptiometry. Physical activity was assessed by quantitative and semiquantitative questionnaires. Data on dietary intake, socioeconomic status, smoking status, and use of hormone replacement therapy (HRT) were also gathered. RESULTS: Total-body and abdominal central adiposity were lower with higher levels of home, sporting, and sweating-associated activity. Total-body and central abdominal fat were 5.6 kg and 0.44 kg lower, respectively, in participants who reported vigorous weight-bearing activity. Physical activity was the strongest independent predictor of total-body fat (beta = -0.6 [CI, -1.06 to -0.15]; P = 0.009) and central abdominal fat (beta = -0.07 [CI, -0.1 to -0.03]; P < 0.001) in a regression model that included age, diet, smoking, HRT use, and socioeconomic status. Monozygotic twin pairs who were concordant for smoking and HRT status but were discordant for moderate-intensity sport showed greater within-pair differences in total-body fat than those who were concordant for activity level. In this model, 1 and 2 hours of moderate-intensity sport accounted for within-pair differences of 1.0 kg (P = 0.050) and 1.4 kg (P = 0.040), respectively, of total-body fat. In participants who had an overweight twin, higher levels of physical activity were still associated with 3.96-kg lower total-body fat and 0.53-kg lower central abdominal fat. CONCLUSIONS: Current physical activity predicts lower total-body and central abdominal adiposity in healthy middle-aged women. After controlling for genetic and environmental factors, the influence of physical activity was greater than that of other measured environmental factors. Participants with a genetic predisposition to adiposity did not show a lesser effect of physical activity on body fat mass.

Abdomen↗

PubMed1998

Genotypic relative risks under ordered restriction.

In mapping diseases of complex aetiology, conventional linkage approaches narrow the location of the disease susceptibility locus to quite a large region so that candidate gene association studies are then necessary to further isolate these genes. However, even in the simplest scenario where the candidate locus is bi-allelic, two statistical tests with various correcting factors have been proposed: a chi-square 1 df test (counting chromosomes) which may be slightly conservative and a 2 df chi-square test (counting genotypes) which may lack power because of the extra degree of freedom. This paper introduces a better and more powerful alternative which turns out to be a compromise between the two existing statistical tests. The asymptotic distribution of this test statistic is determined and the efficacy of the 3 tests are compared under different genetic models by simulation.

Breast Neoplasms↗

PubMed1998

Tobacco smoking and oestrogen replacement are associated with lower total and central fat in monozygotic twins.

BACKGROUND: The known postmenopausal increase in cardiovascular risk may relate in part to changes in fat distribution. Environmental factors which are known to influence cardiovascular disease risk may do so in part by influencing body fat and its distribution. OBJECTIVES: To determine the relationships between tobacco smoking, oestrogen replacement (ERT) and body fat and its distribution in postmenopausal women, independent of genetic factors, physical activity, diet composition and socioeconomic factors. DESIGN: Cross-sectional study in normal post menopausal twins. SUBJECTS: 712 postmenopausal female twins (aged 58.7 +/- 0.2 y, body mass index (BMI) 24.4 +/- 0.1 kg/m2). MEASUREMENTS: Anthropometry; body composition and fat distribution by dual energy x-ray absorptiometry; physical activity, muscle strength, socioeconomic status, dietary composition and dehydroepiandrosterone sulfate (DHEAS). RESULTS: In monozygotic pairs discordant for smoking, intrapair differences in total and central fat were greater than that in concordant pairs, with the lower fat mass in the smoking twin. Overall, smokers had a lower weight, BMI, total and central abdominal fat, despite a higher total and saturated dietary fat intake and similar DHEAS levels. The reduction in central fat was not independent of that in total fat. In monozygotic twins discordant for ERT-use the intrapair differences in total and central body fat were significantly greater than in concordant pairs, with the lower fat measure in the ERT-using twin. Overall, current ERT-users had similar body weight, BMI and total fat compared to non-users but had lower central fat. There were no differences in activity levels, diet or socioeconomic factors between ERT-users and non-users. CONCLUSIONS: Smoking and ERT-use are associated with lower total and central fat in monozygotic postmenopausal twins. In current smokers, the lower central adiposity appears related to its influence on total body fat. In ERT-users, lower central fat may contribute to the reduced cardiovascular risk associated with postmenopausal oestrogen use.

Body Composition↗

PubMed1998

Fine genetic mapping using haplotype analysis and the missing data problem.

The genetic basis of many human diseases, especially those with substantial genetic determinants, has been identified. Notable amongst others are cystic fibrosis, Huntington's disease and some forms of cancer. However, the detection of genetic factors with more modest effects such as in bipolar disorders and a majority of the cancers, has been more complicated. Standard linkage analysis procedures may not only have little power to detect such genes but they do, at best, only narrow the location of the disease susceptibility gene to a rather large region. Association studies are therefore necessary to further unveil the aetiological relevance of these factors to disease. However, the number of tests required if such procedures were used in extended genome-wide screens, is prohibitive and as such association studies have seen limited application, except in the investigation of candidate genes. In this paper, we discuss a logistic regression approach as a generalization of this procedure so that it can accommodate clusters of linked markers or candidate genes. Furthermore, we introduce an expectation maximization (E-M) algorithm with which to estimate haplotype frequencies for multiple locus systems with incomplete information on phase.

Algorithms↗

PubMed1998

Genes versus environment. The relationship between dietary fat and total and central abdominal fat.

OBJECTIVE: The influence of diet on body fat has not been quantified independently of genetic influences, although both are held to contribute to regulation of body fat stores. This study examined 1) the relationship between recent diet and total body and central abdominal fat in middle-aged female twins independent of genetic and important environmental factors and 2) evidence of interaction between diet and genetic predisposition. RESEARCH DESIGN AND METHODS: Measurements in 436 healthy female twins (aged 58 +/- 10 years) included dietary intake by food frequency questionnaire (validated against a 7-day food diary, n = 162), BMI, total body and central abdominal fat by dual-energy X-ray absorptiometry, and environmental covariates (smoking habit, hormone replacement, and physical activity) by standardized questionnaire. Dietary energy underreporters were excluded. RESULTS: Intake of dietary fat (total and subtype) and carbohydrates was not related to BMI or to total or central fat, confirmed in quintile analysis. With genetic and environmental factors controlled in 90 monozygotic pairs, differences in the intake of energy, fat, or protein were not related to intrapair differences in total and central body fat. However, a minor inverse relationship between carbohydrate intake and total adiposity was confirmed (r = -0.25, P = 0.02). In paired analyses, the twin with the higher intake of total sugars had significantly lower total body and central abdominal adiposity. There was no evidence of a gene-environment interaction between intake of fat or carbohydrates contributing to greater body fat mass in subjects genetically predisposed to obesity. CONCLUSIONS: Using validated dietary measures and direct measures of body fat and excluding underreporters, no relationship between dietary fat and body fat was found in middle-aged women, particularly after controlling for genetic and some environmental factors. The role of dietary factors in determining total body and central abdominal fat appears to have been overestimated in past cross-sectional studies.

Abdomen↗

PubMed1995

Linkage detection under heterogeneity and the mixture problem.

Linkage analysis has contributed to the localization of many human disease genes. The presence of locus heterogeneity reduces statistical power and can prejudice the detection of linkage if the analysis assumes homogeneity. Nevertheless, mixed genetic models are not routinely used in gene searches. The null distribution of the test statistic is not uniquely defined. In this paper, a transformation is used to determine an approximate asymptotic distribution of the test statistic under a mixture model. The equivalent critical values of the test are computed and the performance of the test under various levels of heterogeneity and family size is investigated. For gene searches, we recommend the routine use of an admixture model with a critical lod score of 3.44.

Algorithms↗

PubMed1994

Bootstrapping in human genetic linkage.

Linkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.

Chromosome Mapping↗