General practitioners' views on genomics, practice and education: A qualitative interview study.

BACKGROUND AND OBJECTIVES: Genomics is moving rapidly into mainstream medicine through clinical genomic testing and consumer-initiated online DNA testing. The aim of this study was to identify Australian general practitioners' (GPs') views on genomics, impact on practice and educational needs to inform continuing education. METHOD: Semi-structured interviews were conducted, with constant comparative inductive analysis and governance from a national taskforce. RESULTS: Twenty-eight GPs (43% female) were interviewed; 71% worked in a metropolitan workplace. Most initially reported little experience with genetic/genomic tests but, when prompted, recognised encountering genomics, mainly non-invasive prenatal and single-gene tests. Many GPs referred patients for cancer screening to genetic services or specialists. GPs reported needing continuing education and resources, with preferences underpinned by relevance to practice. DISCUSSION: GPs are integrating genomic testing into care, mainly through prenatal screening, and anticipate further impact. They want diverse and context-dependent education but are unaware of some available resources, such as The Royal Australian College of General Practitioners' Genomics in general practice guideline.

The expectations and realities of nutrigenomic testing in australia: A qualitative study.

BACKGROUND: Consumer genomic testing for nutrition and wellness, (nutritional genomics), is becoming increasingly popular. Concurrently, health-care practitioners (HPs) working in private practice (including doctors interested in integrative medicine, private genetic counsellors, pharmacists, dieticians, naturopaths and nutritionists) are involved as test facilitators or interpreters. OBJECTIVE: To explore Australian consumers' and HPs' experiences with nutrigenomic testing. METHOD: Semi-structured in-depth interviews were conducted using predominantly purposive sampling. The two data sets were analysed individually, then combined, using a constant comparative, thematic approach. RESULTS: Overall, 45 interviews were conducted with consumers (n = 18) and HPs (n = 27). Many of the consumer interviewees experienced chronic ill-health. Nutrigenomic testing was perceived as empowering and a source of hope for answers. While most made changes to their diet/supplements post-test, self-reported health improvements were small. A positive relationship with their HP appeared to minimize disappointment. HPs' adoption and views of nutrigenomic testing varied. Those enthusiastic about testing saw the possibilities it could offer. However, many felt nutrigenomic testing was not the only 'tool' to utilize when offering health care. DISCUSSION: This research highlights the important role HPs play in consumers' experiences of nutrigenomics. The varied practice suggests relevant HPs require upskilling in this area to at least support their patients/clients, even if nutrigenomic testing is not part of their practice. PATIENT OR PUBLIC CONTRIBUTION: Advisory group included patient/public group representatives who informed study design; focus group participants gave feedback on the survey from which consumer interviewees were sourced. This informed the HP data set design. Interviewees from HP data set assisted with snowball sampling.

From Expectations to Experiences: Consumer Autonomy and Choice in Personal Genomic Testing.

Background: Personal genomic testing (PGT) offers individuals genetic information about relationships, wellness, sporting ability, and health. PGT is increasingly accessible online, including in emerging markets such as Australia. Little is known about what consumers expect from these tests and whether their reflections on testing resonate with bioethics concepts such as autonomy.Methods: We report findings from focus groups and semi-structured interviews that explored attitudes to and experiences of PGT. Focus group participants had little experience with PGT, while interview participants had undergone testing. Recordings were transcribed and analyzed using thematic analysis. Findings were critically interpreted with reference to bioethics scholarship on autonomy.Results: Fifty-six members of the public participated in seven focus groups, and 40 individuals were interviewed separately. Both groups valued the choice of PGT, and believed that it could motivate relevant actions. Focus group themes centered on the perceived value of choices, knowledge enabling action and knowledge about the self. Interview themes suggest that participants reflexively engage with their PGT information to make meaning, and that some appreciate its shortcomings. Critical interpretation of findings shows that while consumers of PGT are able to exercise a degree of autonomy in choosing, they may not be able to achieve a substantive conceptualization of autonomy, one that promotes alignment with higher-order desires.Conclusions: PGT consumers can critically reason about testing. However, they may uncritically accept test results, may not appreciate drawbacks of increased choice, or may overestimate the potential for information to motivate behavioral change. While consumers appear to be capable of substantive autonomy, they do so without ongoing support from companies. PGT companies promote a problematic ("default") account of autonomy, reliant on empowerment rhetoric. This leaves consumers vulnerable to making decisions inconsistent with their higher-order desires. As PGT expands, claims about its power and value need to be carefully drawn.

Significantly Elevated FMR1 mRNA and Mosaicism for Methylated Premutation and Full Mutation Alleles in Two Brothers with Autism Features Referred for Fragile X Testing.

Although fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥200 cytosine-guanine-guanine (CGG) repeats, and a decrease in FMR1 mRNA and its protein (FMRP), incomplete silencing has been associated with more severe autism features in FXS males. This study reports on brothers (B1 and B2), aged 5 and 2 years, with autistic features and language delay, but a higher non-verbal IQ in comparison to typical FXS. CGG sizing using AmplideX PCR only identified premutation (PM: 55-199 CGGs) alleles in blood. Similarly, follow-up in B1 only revealed PM alleles in saliva and skin fibroblasts; whereas, an FM expansion was detected in both saliva and buccal DNA of B2. While Southern blot analysis of blood detected an unmethylated FM, methylation analysis with a more sensitive methodology showed that B1 had partially methylated PM alleles in blood and fibroblasts, which were completely unmethylated in buccal and saliva cells. In contrast, B2 was partially methylated in all tested tissues. Moreover, both brothers had FMR1 mRNA ~5 fold higher values than those of controls, FXS and PM cohorts. In conclusion, the presence of unmethylated FM and/or PM in both brothers may lead to an overexpression of toxic expanded mRNA in some cells, which may contribute to neurodevelopmental problems, including elevated autism features.

Personal genomic testing for nutrition and wellness in Australia: A content analysis of online information.

AIM: Personal genomic testing for nutrition and wellness (PGT-NG) offers a new service delivery model to nutritionists and dietitians. However, research indicates that this type of testing currently lacks sufficient clinical validity and utility to be commercially available. Despite Australian guidelines to the contrary, healthcare professionals are currently offering testing to clients, and promoting these services online. Thus, it is important to understand how PGT-NG is currently framed online to the public. METHODS: A mixed methods content analysis was conducted to assess the content, quality and marketing approaches of websites offering PGT-NG to Australians. Websites were identified using popular search engines to mimic the behaviour of a consumer. A novel framework was developed for the purposes of the analysis. RESULTS: Thirty-nine websites were analysed, comprising four nutritional genomic testing company websites and 35 healthcare provider websites. Healthcare providers relied on information from the testing companies. The content was emotive, and little attention was given to the scientific and ethical aspects of personal genomic testing. Websites appealed to consumer empowerment and framed testing as an essential and superior tool for optimising health. CONCLUSIONS: Websites lacked the transparency necessary for informed consent. A basic checklist of key information was developed to aid healthcare providers when informing potential clients of PGT-NG online.

Australians' views and experience of personal genomic testing: survey findings from the Genioz study.

Personal genomic tests (PGTs) for multiple purposes are marketed to ostensibly healthy people in Australia. These tests are generally marketed and purchased online commercially or can be ordered through a health professional. There has been minimal engagement with Australians about their interest in and experience with ordering a PGT. As part of a multistage, interdisciplinary project, an online survey (Stage 2 of the Genioz study) was available from May 2016 to May 2017. In total, 3253 respondents attempted the survey, with 2395 completed Australian responses from people with and without experience of having a PGT: 72% were female; 59% of the whole sample were undertaking/or had a university education; and, overall, age ranged from 18-over 80. A total of 571 respondents reported having had a genetic test, 373 of these classifiable as a PGT. A bivariate analysis suggests people who have undergone PGT in our sample were: women aged 25 and over; or in a high socioeconomic group, or have a personal or family diagnosis of a genetic condition (P ≤ 0.03). After a multivariate analysis, socioeconomic status and a genetic condition in the family were not of significance. The most common types of PGT reported were for carrier status and ancestry. Findings suggest greater awareness of, and an increasing demand for non-health related PGT in Australia. To support both consumers and health care professionals with understanding PGT results, there is a need for appropriate support and resources.

Australians' perspectives on support around use of personal genomic testing: Findings from the Genioz study.

Personal genomic testing using direct-to-consumer and consumer-directed models, with or without involvement of healthcare providers, is increasing internationally, including in Australia. This study forms a sub-set of the Genioz study - Genomics: National Insights of Australians. We aimed to explore Australians' experiences with these types of tests, especially online DNA tests, and their views regarding whom they would seek support from around understanding test results. The study used a mixed methods approach, employing an exploratory quantitative online survey and follow-up qualitative semi-structured interviews. Between May 2016 and May 2017, 2841 Australians responded to the survey. Interviews were conducted with 63 purposively sampled respondents, including 45 who had a genetic test and 18 who had not. Of 571 respondents who had any type of genetic test, 322 had a personal genomic test using criteria defined by the researchers. Testing for ancestry/genealogy was the most common, reported by 267 participants, reflecting the increased advertising of these tests in Australia. Some respondents described downloading their raw data for further interpretation through third party websites for genealogical as well as health related information. Carrier testing, testing for serious and preventable conditions and nutrition and/or wellness were the most common health related tests reported by respondents. Participants generally preferred to seek support from general practitioners (GPs), medical specialists with relevant expertise and independent genetics specialists, although another important preference for non-health information was online forums and networks. There was less preference for seeking support from employees associated with the testing companies. Generally, of those who had a health related PGT, the most common actions were seeking medical advice or doing nothing with the information, while more of those who had a personal genomic test for nutrition and/or wellness sought advice from complementary/alternative health practitioners (eg naturopaths) and integrative GPs, and 60% reported they had changed their diet. As awareness of personal genomic testing increases, publicly funded clinical genetics services may be less inclined to discuss results from personal genomic testing. Genetic counsellors could play an important role in providing this support, both pre-test and post-test, through opportunities for private practice but independent from testing companies.

Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes.

BACKGROUND: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders that are caused by abnormal expression of imprinted genes in the 15q11-13 region. Dysregulation of genes located in this region has been proposed as a susceptibility factor for autism spectrum disorder (ASD) in both disorders. METHODS: This study aimed to explore symptoms of ASD in 25 PWS and 19 AS individuals aged between 1 and 39 years via objective assessment. Participants completed the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) and a developmentally or age-appropriate intellectual functioning assessment. All participants had their genetic diagnosis confirmed using DNA methylation analysis and microarray testing of copy number changes within the 15q11-13 region. RESULTS: Participants with PWS had significantly higher overall and social affect calibrated severity scores (CSS) on the ADOS-2 compared to AS participants (p = .0055 and .0015, respectively), but the two groups did not differ significantly on CSS for the repetitive and restricted behaviour domain. CONCLUSIONS: PWS cases presented with greater symptoms associated with ASD compared to individuals with AS. Mental health issues associated with PWS may contribute to elevated symptoms of ASD, particularly in adolescents and adults with PWS.

Australians' views on personal genomic testing: focus group findings from the Genioz study.

Personal genomic testing provides healthy individuals with access to information about their genetic makeup for purposes including ancestry, paternity, sporting ability and health. Such tests are available commercially and globally, with accessibility expected to continue to grow, including in Australia; yet little is known of the views/expectations of Australians. Focus groups were conducted within a multi-stage, cross-disciplinary project (Genioz) to explore this. In mid-2015, 56 members of the public participated in seven focus groups, allocated into three age groups: 18-24, 25-49, and ≥50 years. Three researchers coded transcripts independently and generated themes. Awareness of personal genomic testing was low, but most could deduce what "personal genomics" might entail. Very few had heard of the term "direct-to-consumer" testing, which has implications for organisations developing information to support individuals in their decision-making. Participants' understanding of genetics was varied and drawn from several sources. There were diverse perceptions of the relative influence of genetics and environment on health, mental health, behavior, talent, or personality. Views about having a personal genomic test were mixed, with greater interest in health-related tests if they believed there was a reason for doing so. However, many expressed scepticisms about the types of tests available, and how the information might be used; concerns were also raised about privacy and the potential for discrimination. These exploratory findings inform subsequent stages of the Genioz study, thereby contributing to strategies of supporting Australians to understand and make meaningful and well-considered decisions about the benefits, harms, and implications of personal genomic tests.

Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X.

Increased intragenic DNA methylation of the Fragile X Related Epigenetic Element 2 (FREE2) in blood has been correlated with lower intellectual functioning in females with fragile X syndrome (FXS). This study explored these relationships in a paediatric cohort of males with FXS using Buccal Epithelial Cells (BEC). BEC were collected from 25 males with FXS, aged 3 to 17 years and 19 age-matched male controls without FXS. Methylation of 9 CpG sites within the FREE2 region was examined using the EpiTYPER approach. Full Scale IQ (FSIQ) scores of males with FXS were corrected for floor effect using the Whitaker and Gordon (WG) extrapolation method. Compared to controls, children with FXS had significant higher methylation levels for all CpG sites examined (p < 3.3 × 10-7), and within the FXS group, lower FSIQ (WG corrected) was associated with higher levels of DNA methylation, with the strongest relationship found for CpG sites within FMR1 intron 1 (p < 5.6 × 10-5). Applying the WG method to the FXS cohort unmasked significant epi-genotype-phenotype relationships. These results extend previous evidence in blood to BEC and demonstrate FREE2 DNA methylation to be a sensitive epigenetic biomarker significantly associated with the variability in intellectual functioning in FXS.

Informed decision making and psychosocial outcomes in pregnant and nonpregnant women offered population fragile X carrier screening.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (χ2=16.98, P<0.001). Overall, informed choice was high in both nonpregnant (77.4%) and pregnant (72.9%) women (χ2=0.21, P=0.644), and more tested (76.0%) than not-tested (66.7%) women (χ2=6.35, P=0.012) made an informed choice. Measures of depression, stress, and anxiety were similar to population norms for ~85% of women. Decisional conflict and regret were generally low; however, decisional uncertainty and regret were greater in pregnant than nonpregnant women, and not-tested than tested women (uncertainty: χ2=18.51, P<0.001 and χ2=43.11, P<0.001, respectively; regret: χ2=6.61, P<0.037 and χ2=35.54, P<0.001, respectively).ConclusionWe provide evidence to inform guidelines that population FXS carrier screening can be implemented with minimal psychosocial harms following appropriate information and prescreening genetic counseling.

Consumer Health Informatics Aspects of Direct-to-Consumer Personal Genomic Testing.

This paper uses consumer health informatics as a framework to explore whether and how direct-to-consumer personal genomic testing can be regarded as a form of information which assists consumers to manage their health. It presents findings from qualitative content analysis of web sites that offer testing services, and of transcripts from focus groups conducted as part a study of the Australian public's expectations of personal genomics. Content analysis showed that service offerings have some features of consumer health information but lack consistency. Focus group participants were mostly unfamiliar with the specifics of test reports and related information services. Some of their ideas about aids to knowledge were in line with the benefits described on provider web sites, but some expectations were inflated. People were ambivalent about whether these services would address consumers' health needs, interests and contexts and whether they would support consumers' health self-management decisions and outcomes. There is scope for consumer health informatics approaches to refine the usage and the utility of direct-to-consumer personal genomic testing. Further research may focus on how uptake is affected by consumers' health literacy or by services' engagement with consumers about what they really want.

Experiences of prenatal diagnosis and decision-making about termination of pregnancy: A qualitative study.

BACKGROUND: Advances in genetic technologies and ultrasound screening techniques have increased the ability to predict and diagnose congenital anomalies during pregnancy. As a result more prospective parents than ever before will receive a prenatal diagnosis of a fetal abnormality. Little is known about how Australian women and men experience receiving a prenatal diagnosis and how they make their decision about whether or not to continue the pregnancy. AIMS: This qualitative study aims to describe parental experiences and examine how best to provide support after a prenatal diagnosis. RESULTS: Individual in-depth interviews were conducted with 102 women and men approximately six weeks post-diagnosis of fetal abnormality. Data were elicited using a narrative, chronological approach and women (n = 75) and a sample of male partners (n = 27) were separately interviewed. Thematic analysis, involving a rigorous process of qualitative coding, enabled iterative development and validation of emergent themes. Participants identified that the shock of the diagnosis can be lessened when good care is delivered, by provision of: clear, accurate and respectful communication; empathic, non-judgemental, professional support; timely access to further testing and appointments; seamless interactions with services and administration; appropriate choices about invasive testing; acknowledgment of the enormity and unexpected nature of the diagnosis, and of the subsequent decision-making challenges; and discussion of the myriad feelings likely to emerge throughout the process. CONCLUSIONS: This study has demonstrated the importance of providing timely access to accurate information and supportive, non-judgemental care for women and their partners following prenatal diagnosis of a fetal abnormality.

"It gives them more options": preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare.

This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an in-depth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community.

A mixed methods exploration of families' experiences of the diagnosis of childhood spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with a carrier frequency of 1 in 41 in Australia. Childhood SMA is classified into three types based on the age at which children present with symptoms and the clinical severity. Families' experiences leading up to the diagnosis have not been described, but are important when considering the potential for a diagnostic odyssey. Using a mixed methods approach, data were collected from interviews and a national survey of families of children with SMA to explore their experiences of this journey. The combined findings (n=28) revealed that the journey to receiving a diagnosis was protracted. The time from first noticing symptoms to finally receiving a diagnosis was emotional and frustrating. Once parents or other family members became aware of symptoms, almost all had consulted with multiple different health professionals before the diagnosis was ultimately made. Not surprisingly, receiving the diagnosis was devastating to the families. The nature of the information and the way it was given to them was not always optimal, particularly because of the difficulties predicting clinical severity. Most felt that their child could have been diagnosed earlier and, although there were mixed views around the benefit of this for their child, they felt it may have reduced the emotional impact on families. Overall, families were more in favour of population carrier screening for SMA when compared with newborn screening of the population. Despite an increasing awareness of SMA, the diagnostic delay continues to have negative impacts on families.

"It's about having the choice": stakeholder perceptions of population-based genetic carrier screening for fragile X syndrome.

This project explored, the views of key stakeholders regarding population-based genetic carrier screening for fragile X syndrome (FXS). Interviews and focus groups were conducted with healthcare providers, relatives of individuals with FXS and members of the general population. Data were transcribed verbatim and coded into themes. 188 individuals took part in this study. Perceived benefits of carrier screening included: learning the risk of having a child with FXS; learning the risk of fragile X-associated primary ovarian insufficiency; and the opportunity for carriers to access reproductive options. Concerns included: the emotional impact of screening and receiving a carrier result; the predictive testing nature of the carrier test with respect to fragile X-associated tremor/ataxia syndrome; potential confusion created by receiving an intermediate result; and implications of genetic screening for society. Overall, population-based genetic carrier screening was perceived to be acceptable provided it is optional and offered at an appropriate stage of life. With the support of the participants to promote individual choice by offering a population-based carrier screening program for FXS, it is essential to carefully consider how screening might be offered in order to ensure broad accessibility and facilitation of decision-making.

ironXS: high-school screening for hereditary haemochromatosis is acceptable and feasible.

As the results of the Human Genome Project are realised, screening for genetic mutations that predispose to preventable disease is becoming increasingly possible. How and where such screening should best be offered are critical, unanswered questions. This study aimed to assess the acceptability and feasibility of genetic screening for preventable disease, using the model of hereditary haemochromatosis, in high-school students. Screening was offered for the HFE C282Y substitution to 17,638 students. Questionnaires were administered at the time of screening (Q1) and approximately 1 month after results were communicated (Q2). Outcomes assessed were uptake of screening, change in scores of validated anxiety, affect and health perception scales from Q1 to Q2, knowledge and iron indices in C282Y homozygous individuals. A total of 5757 (32.6%) students had screening and 28 C282Y-homozygous individuals (1 in 206) were identified, and none of the 27 individuals who had iron indices measures had significant iron overload. There was no significant change in measures of anxiety, affect or health perception in C282Y homozygous or non-homozygous individuals. Over 86% of students answered each of five knowledge questions correctly at Q1. Genetic population-based screening for a preventable disease can be offered in schools in a way that results in minimal morbidity for those identified at high risk of disease. The results of this study are not only relevant for haemochromatosis, but for other genetic markers of preventable disease such as those for cardiovascular disease and cancer.

"Did you find that out in time?": new life trajectories of parents who choose to continue a pregnancy where a genetic disorder is diagnosed or likely.

The availability of tests to detect genetic conditions prenatally has expanded considerably in recent decades. These advances allow women and couples choices; the choice of whether or not to undergo prenatal screening or diagnosis and therefore the choice whether to continue or terminate a pregnancy. Following prenatal testing many people choose to terminate an affected pregnancy, however little is known about the experiences of parents who choose to continue such a pregnancy. This exploratory qualitative study involved in-depth interviews with five mothers and four fathers who experienced a pregnancy where a genetic diagnosis was, or could have been, detected prenatally. Transcripts of the interviews were analyzed using thematic analysis. While the participants' experiences of genetic diagnoses and prenatal choices varied, findings revealed three major categories triggering new life trajectories for all of these parents: knowledge of reproductive risk and receiving a genetic diagnosis; adapting to diagnosis and new life path; and attitudes to prenatal diagnosis and disability. Parents reported that while dealing with their own attitudes and getting on with their "new world," positive and negative attitudes of others impacted on these parents' experiences. A conceptual model arising from the major themes is offered as a way of thinking about this paradigm. Parents who continue a pregnancy where a genetic condition is detected or suspected prenatally, can be supported appropriately by health professionals while adjusting to their new life path.