Regressive logistic and proportional hazards disease models for within-family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer

Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5UTR TC MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.

Genetic variation in SH3-domain GRB2-like (endophilin)-interacting protein 1 has a major impact on fat mass

Objective:

The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease.
Subjects:

We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass.
Results:

Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10−5). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele.
Conclusions:

Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.

Socioeconomic position in young adulthood is associated with BMI in Australian families

BACKGROUND: Low socioeconomic position (SEP) is associated with increased cardiovascular (CV) disease risk, but the relative importance of SEP in childhood and adulthood, and of changes in SEP between these two life stages, remains unclear. Studies of families may help clarify these issues. We aimed to assess whether SEP in young adulthood, or change in SEP from childhood to young adulthood, was associated with five continuously measured CV risk factors. METHODS: We used data from 286 adult Australian families from the Victorian Family Heart Study (VFHS), in which some offspring have left home (n = 364) and some remained at home (n = 199). SEP (defined as the Index of Relative Socioeconomic Disadvantage) was matched to addresses. We fitted variance components models to test whether young adult SEP and/or change in SEP was associated with systolic blood pressure, diastolic blood pressure, body mass index (BMI), total cholesterol or high-density lipoprotein cholesterol, after adjustment for parental SEP and within-family correlation. RESULTS: An increase in SEP of 100 SEIFA units from childhood to adulthood was associated with a lower BMI (β = -0.49 kg/m(2), P < 0.01) only. CONCLUSIONS: These results suggest that a change in SEP in young adulthood is an important predictor of BMI, independent of childhood SEP.

iPrevent®: a tailored, web-based, decision support tool for breast cancer risk assessment and management

We aimed to develop a user-centered, web-based, decision support tool for breast cancer risk assessment and personalized risk management. Using a novel model choice algorithm, iPrevent(®) selects one of two validated breast cancer risk estimation models (IBIS or BOADICEA), based on risk factor data entered by the user. Resulting risk estimates are presented in simple language and graphic formats for easy comprehension. iPrevent(®) then presents risk-adapted, evidence-based, guideline-endorsed management options. Development was an iterative process with regular feedback from multidisciplinary experts and consumers. To verify iPrevent(®), risk factor data for 127 cases derived from the Australian Breast Cancer Family Study were entered into iPrevent(®), IBIS (v7.02), and BOADICEA (v3.0). Consistency of the model chosen by iPrevent(®) (i.e., IBIS or BOADICEA) with the programmed iPrevent(®) model choice algorithm was assessed. Estimated breast cancer risks from iPrevent(®) were compared with those attained directly from the chosen risk assessment model (IBIS or BOADICEA). Risk management interventions displayed by iPrevent(®) were assessed for appropriateness. Risk estimation model choice was 100 % consistent with the programmed iPrevent(®) logic. Discrepant 10-year and residual lifetime risk estimates of >1 % were found for 1 and 4 cases, respectively, none was clinically significant (maximal variation 1.4 %). Risk management interventions suggested by iPrevent(®) were 100 % appropriate. iPrevent(®) successfully integrates the IBIS and BOADICEA risk assessment models into a decision support tool that provides evidence-based, risk-adapted risk management advice. This may help to facilitate precision breast cancer prevention discussions between women and their healthcare providers.

Family and home correlates of television viewing in 12-13 year old adolescents: the Nepean study

Background
Few young people meet television viewing guidelines.
Purpose
To determine the association between factors in the family and home environment and watching television, including videos and DVDs, in early adolescence.
Methods
Cross-sectional, self-report survey of 343 adolescents aged 12–13 years (173 girls), and their parents (338 mothers, 293 fathers). Main measures were factors in the family and home environment potentially associated with adolescents spending ≥ 2 hours per day in front of the television. Factors examined included family structure, opportunities to watch television/video/DVDs, perceptions of rules and regulations on television viewing, and television viewing practices.
Results
Two-thirds of adolescents watched ≥ 2 hours television per day. Factors in the family and home environment associated with adolescents watching television ≥ 2 hours per day include adolescents who have siblings (Adjusted Odds Ratio [95%CI] AOR = 3.0 [1.2, 7.8]); access to pay television (AOR = 2.0 [1.1, 3.7]); ate snacks while watching television (AOR = 3.1 [1.8, 5.4]); co-viewed television with parents (AOR = 2.3 [1.3, 4.2]); and had mothers who watched ≥ 2 hours television per day (AOR = 2.4 [1.3, 4.6]).
Conclusion
There are factors in the family and home environment that influence the volume of television viewed by 12–13 year olds. Television plays a central role in the family environment, potentially providing a means of recreation among families of young adolescents for little cost. Interventions which target family television viewing practices and those of parents, in particular, are more likely to be effective than interventions which directly target adolescent viewing times.

Parents with psychosis : a pilot study examining self-report measures related to family functioning

The aims of this study were to examine the utility of various self-report instruments related to family functioning in families where a parent has a psychotic disorder, and to explore associations between these instruments and symptoms in the parent. Twenty-one parents with a psychotic disorders participated in the study. All participants were able to complete the questionnaires and the majority of parents reported levels of parental competence in the average range. Most parents (90%) perceived themselves to be effective parents, however 30% reported low levels of satisfaction with the parenting role. There were significant associations between objective measures of negative symptoms and self-report scores related to problems in ways of coping, and problems with parent-child interactions. Many individuals with psychosis were able to report areas of perceived need related to their role as parents and to the functioning of their families, however there are several limitations in the use of these instruments in this setting.

Family recovery from youth substance use related problems : a pilot study of the BEST plus program

Youth substance use related problems are increasingly common, and families experience considerable stress in attempting to cope with these problems. A pilot study of 34 Australian parents from 21 families (38% sole parent families) participating in an 8-week group program, designed to assist families recover from youth substance use related problems, provided the context to explore family change processes. Participants reported a number of significant improvements over the course of the four groups that ran from late 2003 and through 2004. Regression analyses found general support for the program logic model in identifying significant associations between program-targeted parent changes and post-program improvements in stress symptoms and cohesive family behaviors. The study's limitations are noted.

Impact of the extended family on microenterprise growth in Ghana : a case study of Accra

This study examines the extended family's impact on microenterprise growth at the individual level, where microenterprise operators have some control over constraints affecting their operations. Beyond the individual level, microenterprise operators have little control over constraints such as government policies and regulations, competition from import-substitution industries and exploitation by corrupt officials. Therefore, it is at the individual level that the extended family serves as a crucial parameter of microenterprise growth and the success with which MEs graduate from the informal sector into the mainstreams of small business. Within this domain, this author has examined the extended family and found that there is a need for policy makers and MED administrators to adopt a more culturally sensitive approach to microenterprise growth if the extended family is to be engaged as a partner in their efforts to support microenterprises as a source of income and employment generation, A central question posed is why most writers on microenterprise activities in Ghana have neglected the extended family as a factor that should be considered in the design of microenterprise growth strategies and policies? The answer to this question was explored in the process of data gathering for this thesis and the results are presented here, especially in chapter 3 below. Suffice it to note here that this neglect has many roots, not least of which is the proclivity of mainstream economics, modern administration practice and the objectivity of double entry accounting based documentation procedures to focus on measurable growth in the formal sectors of the economy and structural constraints such as the lack of finance, lack of market demand, lack of access to technology and government regulations. Consequently, a noticeable trend among these writers is that they rightly advocate finance be made accessible to microenterprises, however, few question whether the finance is effectively used towards microenterprise growth. This issue is crucial in the face of evidence from this study which shows that finance accessed towards microenterprise growth is often put to other uses that negate growth thus keeping microenterprises within the bounds of the informal sector as against graduating out of the informal sector. As a result, these writers have neglected the intimate relations between the extended family and microenterprises, and most importantly, the constraint that the extended family inflicts on microenterprise growth at the individual level of activity. This study, by targeting the growth of the individual microenterprise in the socio-cultural context in which this growth must be achieved, has highlighted the constraint that the extended family does pose on MED. However, the study also shows that these constraints are important not because there is anything inherently wrong with the extended family, but because the socio-economic and policy environment is not consistent with the positive role that the extended family can and should play in the graduation of microenterprises from the informal to the formal sector of the economy in Ghana.

Crisis in Clio's family : a study of the discipline of Australian economic history 1918-1965

This thesis presents an intellectual history of the historiography of Australian Economic History between 1918 and 1965. More specifically, it is a contribution to a relatively novel area of research into 'disciplinary history’. It takes as its basic analytical material the four books widely used for significant lengths of time for undergraduate teaching during the period of the study. The thesis consists of five main chapters, plus an appendix which surveys the institutional development of Australian Economic History and provides the empirical basis for the selection of the works named above. After a brief introduction and overview, the next four chapters consist of a detailed study of one of these works, the historical context in which each was written, and an intellectual biography. The fifth chapter is largely theoretical and conceptual. It analyses the epistemological bases of History and Economics and explores the implications of different models of knowledge for the relationship between Economic History and its two antecedent disciplines, History and Economics. Current perceptions of the state of the discipline in Australia and overseas are also examined. There are three main propositions advanced and their implications explored in the fifth chapter. First, that changes which occurred in Australian Economic History during the period 1918-1965 shifted the discipline from the broad area of History to the broad area of Economics. Second, that the inherent tension and fundamental differences between the two disciplinary areas of History and Economics have profound and complex implications for Australian Economic History at a number of levels and in a number of areas. The third proposition posits that the paradigm shift of the 1950s/1960s in Australian Economic History, and the paradigm shift of the 1960s/1970s in Economic History respectively have resulted in crisis. The final part of the chapter summarises the contents of the preceding chapters, and draws some conclusions based on those detailed studies.

Case study demonstration of the family context of anxiety disorders across the lifespan and the effectiveness of cognitive-behavioural interventions

This portfolio aims to explore some of the issues related to the treatment of anxiety disorders in clinical practice by reviewing the literature on anxiety disorders across the lifespan and presenting four clinical case studies of individuals with different anxiety disorders.

Child focused and child inclusive family law dispute resolution : one year findings from a prospective study of outcomes

This prospective study compared outcomes over 1 year for two groups of separated parents, who attended mediation about their entrenched parenting disputes. The two treatments studied both aimed to improve the psychological resolution of parental conflict with associated reduction of distress for their children. The Child Focused intervention prioritised thought about the needs of children in high conflict divorce, but without any direct involvement of the children, while the Child Inclusive intervention incorporated separate consultation by a specialist with the children in each family, and consideration of their concerns with parents in the mediation forum. Measures were collected from parents and children prior to mediation commencing, and again three and twelve months after the conclusion of mediation. Significant and enduring reduction in levels of conflict and improved management of disputes occurred for both treatment groups in the year after mediation. Across all ages, children in both interventions perceived less frequent and intense conflict between their parents and better resolution of it, with a significant lowering of their related distress. The Child Inclusive intervention showed a number of independent effects not evident in the other treatment group, related to relationship improvements and psychological wellbeing. These effects were strongest for fathers and children. Agreements reached by the Child Inclusive group were significantly more durable and workable over the year, and these parents were half as likely to instigate new litigation over parenting matters in the year after mediation than were the Child Focused parents. The article considers possible mechanisms of change underpinning these outcomes.

Understanding children's sedentary behaviour : a qualitative study of the family home environment

Electronic media (EM) (television, electronic games and computer) use has been associated with overweight and obesity among children. Little is known about the time spent in sedentary behaviour (SB) among children within the family context. The aim of this study was to explore how the family home environment may influence children's electronic-based SB. Focus groups and family interviews were conducted with 11- to 12-year old children (n = 54) and their parents (n = 38) using a semi-structured discussion guide. Transcripts were analysed using a thematic content approach. A brief self-completed questionnaire was also used to measure leisure behaviour and electronic devices at home. Children incorporated both sedentary and physical activities into their weekly routine. Factors influencing children's EM use included parent and sibling modelling and reinforcement, personal cognitions, the physical home environment and household EM use rules and restrictions. Participants were not concerned about the excessive time children spent with EM. This under-recognition emerged as a personal influencing factor and was viewed as a major barrier to modifying children's electronic-based SB. Efforts to reduce SB in children should focus on the influencing factors that reciprocally interact within the family home. An emphasis on increasing awareness about the risks associated with spending excessive time in screen-based activities should be a priority when developing intervention strategies aimed at modifying the time children spend in SB.

A family-based intervention to increase fruit and vegetable consumption in adolescents : a pilot study

Objective: To evaluate the feasibility and effectiveness of a pilot family-based newsletter intervention to increase fruit and vegetable (FV) consumption among adolescents.
Design: Family-based, two-group randomised control trial with baseline, postintervention and follow-up measures. The intervention group received two FV newsletter packs over a 1 month period by postal mail. Social cognitive and behavioural choice theories provide the theoretical framework for the design and development of intervention materials. Control families were provided with all intervention materials at the end of the study. Adolescent FV consumption was assessed by an FFQ. Adolescent-reported barriers to eating FV, FV habits and preferences were the secondary outcomes, along with parent FV consumption, and parents reported knowledge, encouragement, home availability and accessibility of FV. Repeated-measures ANOVA was used to detect differences in behavioural and psychosocial outcomes between groups, time and group-by-time.
Setting: East Midlands, UK.
Subjects: Forty-nine parents and adolescents aged 12–14 years.
Results: Process evaluation indicated high reach, dose acceptability and fidelity of the intervention. At post-intervention and 6 weeks later at follow-up, adolescents in the intervention group had significantly higher fruit: (P0<·01) and vegetable (P<0·05) consumption and higher preferences for vegetables (P<0·01), compared with the control group. At post-intervention and follow-up, parents in the intervention group had significantly higher fruit (P<0·001) and vegetable (P<0·01) consumption and reported higher accessibility of fruit and vegetables (P<0·001), compared with those in the control group.
Conclusions: Family-based, newsletter interventions promoting FV consumption to adolescents appear to be feasible and effective at increasing FV consumption.