Rebekah McWhirter

Community Engagement for Big Epidemiology: Deliberative Democracy as a Tool

Public trust is critical in any project requiring significant public support, both in monetary terms and to encourage participation. The research community has widely recognized the centrality of public trust, garnered through community consultation, to the success of large-scale epidemiology. This paper examines the potential utility of the deliberative democracy methodology within the public health research setting. A deliberative democracy event was undertaken in Tasmania, Australia, as part of a wider program of community consultation regarding the potential development of a Tasmanian Biobank. Twenty-five Tasmanians of diverse backgrounds participated in two weekends of deliberation; involving elements of information gathering; discussion; identification of issues and formation of group resolutions. Participants demonstrated strong support for a Tasmanian Biobank and their deliberations resulted in specific proposals in relation to consent; privacy; return of results; governance; funding; and, commercialization and benefit sharing. They exhibited a high degree of satisfaction with the event, and confidence in the outcomes. Deliberative democracy methodology is a useful tool for community engagement that addresses some of the limitations of traditional consultation methods.

New avenues within community engagement: addressing the ingenuity gap in our approach to health research and future provision of health care

The proliferation of large biorepositories and the staggering advances in our ability to analyse large numbers of human genomes relatively quickly and cost-effectively have been important drivers in the move towards personalised medicine. However, our advances in the development of these tools have outstripped our performance in addressing the issues of ethics and consent surrounding health policy and governance of such repositories, the implications of proliferation of genomic information for the individual and its potential for misuse. Public consultation is urgently needed in the development of ethical guidelines for these emergent issues; however, effective strategies for facilitating community engagement and informed debate have been lacking. Public consultation through deliberative democracy is bringing an essential new dimension to public engagement in the genomic medicine era.

Evidence for a common genetic aetiology in high‐risk families with multiple haematological malignancy subtypes

A family history of a haematological malignancy (HM) is known to be a risk factor for HMs. However, collections of large families with multiple cases of varied disease types are relatively rare. We describe a collection of 12 families with dense aggregations of multiple HM subtypes. Cases were ascertained from a population based study conducted between 1972 and 1980 in Tasmania, Australia. Diagnoses were confirmed through review and re‐examination of stored tissue, pathology reports, Tasmanian Cancer Registry and flow cytometry records. Family trees were generated and kinship coefficients were calculated for all pairs of affected individuals. 120 cases were found in these families. Cases diagnosed with chronic lymphocytic leukaemia (CLL) demonstrated the most significantly increased aggregation (P < 0·0001). There was also significant evidence that those individuals diagnosed at an older age (>53 years), did not aggregate together in families with disease that presented at an earlier age (<20 years) (P = 0·009).

Runs of homozygosity and a cluster of vulvar cancer in young Australian Aboriginal women

OBJECTIVE A cluster of vulvar cancer exists in young Aboriginal women living in remote communities in Arnhem Land, Australia. A genetic case-control study was undertaken involving 30 cases of invasive vulvar cancer and its precursor lesion, high-grade vulvar intraepithelial neoplasia (VIN), and 61 controls, matched for age and community of residence. It was hypothesized that this small, isolated population may exhibit increased autozygosity, implicating recessive effects as a possible mechanism for increased susceptibility to vulvar cancer. METHODS Genotyping data from saliva samples were used to identify runs of homozygosity (ROH) in order to calculate estimates of genome-wide homozygosity. RESULTS No evidence of an effect of genome-wide homozygosity on vulvar cancer and VIN in East Arnhem women was found, nor was any individual ROH found to be significantly associated with case status. This study found further evidence supporting an association between previous diagnosis of CIN and diagnosis of vulvar cancer or VIN, but found no association with any other medical history variable. CONCLUSIONS These findings do not eliminate the possibility of genetic risk factors being involved in this cancer cluster, but rather suggest that alternative analytical strategies and genetic models should be explored.

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders

There is strong evidence for both genetic and environmental risk factors comprising the aetiology of multiple sclerosis (MS). While much progress has been made in recent years in identifying common genetic variants using genome-wide association studies, alternative approaches have remained relatively neglected. The prevalence of MS in Orkney and Shetland is among the highest in the world. Previous studies have suggested that a higher degree of parental relatedness in these isolated communities may contribute to the high rates of MS, indicating that recessive effects have an important role in MS aetiology. The Northern Isles Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age, sex and ancestry, and a further 89 controls matched for sex and ancestry, but passed the majority of lifetime risk of developing MS (>70 years of age). Three participants were removed on the basis of pedigree-genomic anomalies (n=263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.

Identifying public expectations of genetic biobanks.

Understanding public priorities for biobanks is vital for maximising utility and efficiency of genetic research and maintaining respect for donors. This research directly assessed the relative importance the public place on different expectations of biobanks. Quantitative and qualitative results from a national sample of 800 Australians revealed that the majority attributed more importance to protecting privacy and ethical conduct than maximising new healthcare benefits, which was in turn viewed as more important than obtaining specific consent, benefit sharing, collaborating and sharing data. A latent class analysis identified two distinct classes displaying different patterns of expectations. One placed higher priority on behaviours that respect the donor (n = 623), the other on accelerating science (n = 278). Additional expectations derived from qualitative data included the need for biobanks to be transparent and to prioritise their research focus, educate the public and address commercialisation.

The complex genetics of gait speed: Genome-wide meta-analysis approach

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.

Genetic and epigenetic variation in vulvar cancer: current research and future clinical practice.

Vulvar cancer is a relatively rare gynaecological malignancy, the treatment of which is associated with significant patient morbidity. With reports that the incidence of vulvar cancer is increasing, there is a rising need for improved preventive, diagnostic and therapeutic tools. Recent advances within genetics and epigenetics present possible approaches for addressing this need, by contributing to the clarification of the aetiology of this disease, identifying screening and drug targets and introducing the potential for personalised treatments. This paper reviews the genetic and epigenetic research undertaken to date within vulvar cancer, evaluates its potential for clinical application and identifies directions for future research.

Performance data and informed consent: a duty to disclose?

Hospitals, colleges and other institutions increasingly collect, analyse and disseminate data relating to the performance of individual health practitioners, particularly those undertaking surgical procedures. Arguments have long been made for an ethical duty to disclose information regarding a practitioner’s experience or skill to patients as part of the process of informed consent (Box 1).1 Significantly, recent developments suggest that practitioners may, in some circumstances, have a legal duty to disclose their performance data to patients (Box 2).

Genomics in research and health care with Aboriginal and Torres Strait Islander peoples

Abstract Genomics is increasingly becoming an integral component of health research and clinical care. The perceived difficulties associated with genetic research involving Aboriginal and Torres Strait Islander people mean that they have largely been excluded as research participants. This limits the applicability of research findings for Aboriginal and Torres Strait Islander patients. Emergent use of genomic technologies and personalised medicine therefore risk contributing to an increase in existing health disparities unless urgent action is taken. To allow the potential benefits of genomics to be more equitably distributed, and minimise potential harms, we recommend five actions: (1) ensure diversity of participants by implementing appropriate protocols at the study design stage; (2) target diseases that disproportionately affect disadvantaged groups; (3) prioritise capacity building to promote Indigenous leadership across research professions; (4) develop resources for consenting patients or participants from different cultural and linguistic backgrounds; and (5) integrate awareness of issues relating to Indigenous people into the governance structures, formal reviews, data collection protocols and analytical pipelines of health services and research projects.