Melbourne School of Population and Global Health - Research Publications
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ItemNo Preview AvailableExposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.(Environmental Health Perspectives, 1998-04)The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.
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ItemLongitudinal variance components models for systolic blood pressure, fitted using Gibbs sampling(BMC, 2003-12-31)This paper describes an analysis of systolic blood pressure (SBP) in the Genetic Analysis Workshop 13 (GAW13) simulated data. The main aim was to assess evidence for both general and specific genetic effects on the baseline blood pressure and on the rate of change (slope) of blood pressure with time. Generalized linear mixed models were fitted using Gibbs sampling in WinBUGS, and the additive polygenic random effects estimated using these models were then used as continuous phenotypes in a variance components linkage analysis. The first-stage analysis provided evidence for general genetic effects on both the baseline and slope of blood pressure, and the linkage analysis found evidence of several genes, again for both baseline and slope.
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ItemGenome-wide linkage analysis of longitudinal phenotypes using σ2A random effects (SSARs) fitted by Gibbs sampling -: art. no. S12(BMC, 2003-12-31)The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilized data from the longitudinal Framingham Heart Study Family Cohort to investigate the familial aggregation and evidence for linkage to change in systolic blood pressure (SBP) over time. We used Gibbs sampling to derive sigma-squared-A-random-effects (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time) were estimated to account for approximately 9.2% of the variance in the rate of change of SBP with age, while additive genetic effects (sigma2A) were estimated to account for approximately 43.9% of the variance in SBP at the mean age. The linkage results suggested that one or more major loci regulating change in SBP over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results also suggested that one or more major loci regulating level of SBP may localize to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP and change in SBP with age, and are consistent with a complex, multifactorial susceptibility to the development of hypertension. The use of SSARs derived from quantitative traits as input to a conventional linkage analysis appears to be valuable in the linkage analysis of genetically complex traits. We have now demonstrated in this paper the use of SSARs in the context of longitudinal family data.
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ItemNo Preview AvailableLow affinity nerve growth factor receptor gene co-segregates with decreased bodyweight and increased left ventricular weight in spontaneously hypertensive rats(WILEY, 1996)1. The sympathetic nervous system influences the cardiovascular and hormonal systems and sympathetic innervation is dependent on nerve growth factor (NGF). The NGF gene is linked genetically to high blood pressure in the spontaneously hypertensive rat (SHR) and there exists a mutation in the SHR low affinity NGF receptor (LNGFR) gene. 2. To determine whether the LNGFR mutation was linked genetically with cardiovascular phenotypes we studied an F2 population derived from SHR and normotensive Donryu (DRY) rats. 3. Mean arterial pressure (MAP), left ventricular mass (LVM) and related phenotypes were measured in 127 20 week old male F2 rats and correlated with the inheritance of the SHR mutation (S) and/or the DRY allele (D) of the LNGFR. 4. Analysis of variance revealed that the S mutation was associated with a significantly lower bodyweight in F2 rats (P < 0.0001). 5. The S mutation was associated with a significant (P < 0.007) increase in LVM:bodyweight ratio, but not with differences in right ventricular or kidney weights corrected for bodyweight. We found no association between MAP and LNGFR alleles or genotypes. 6. These results suggest that the mutation in the signal peptide of LNGFR may serve as a useful marker for the analysis of genetic factor(s) involved in the differential determination of body size and heart weight.
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ItemFamilies courting the Web: the Internet in the everyday life of household families( 2000)Popular reactions to having the Internet at home include exaggerated fears that families will split up as a result of secret on-line romances and fears that children will learn how to build bombs at home. The Preliminary Stanford Institute Report Internet and Society (2000) which looks at the social consequences of the Internet similarly seems to presume that people are passive consumers of the technology. At the other extreme are studies which suppose that consumers have complete control over the effects of the technology. For example, Silverstone and Hirsch (1992) tend towards a notion of complete agency of the consumer with their model of the appropriation, objectification, incorporation and conversion of information and communication technologies into the household. In this paper, I present findings from a series of in-depth interviews with different types of Australian household families to reveal the diversity of responses to the Internet. Conceiving of the family as a process of continual renegotiation, I theorise the way in which the Internet intersects with the daily life of household families as both an effect of the way in which individuals enact their understanding of family, while simultaneously, use of the Internet enables new performances of the family. Both the technology and the individual members are actors and the performance of family at any time is always an achievement rather than the predictable result of the interaction of the technology with a coherent household.
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ItemThere goes the neighbourhood: the malign effects of stigma(Griffith University, 2006)