Lay Perspectives on Receiving Different Types of Genomic Secondary Findings: a Qualitative Vignette Study.

Genome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics' perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease-cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li-Fraumeni syndrome). Participants (N = 29) wrote down their initial reactions, and discussed (N = 23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual's responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals' reactions to this information.

Genetic predisposition to obesity, restrained eating and changes in body weight: a population-based prospective study.

OBJECTIVES: There is no consensus on whether cognitive control over food intake (that is, restrained eating) is helpful, merely ineffective or actually harmful in weight management. We examined the interplay between genetic risk of obesity, restrained eating and changes in body weight and size. METHODS: Participants were Finnish aged 25-74 years who attended the DIetary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome study at baseline in 2007 and follow-up in 2014. At baseline (n=5024), height, weight and waist circumference (WC) were measured in a health examination and participants self-reported their weight at age 20 years. At follow-up (n=3735), height, weight and WC were based on measured or self-reported information. We calculated 7-year change in body mass index (BMI) and WC and annual weight change from age 20 years to baseline. Three-Factor Eating Questionnaire-R18 was used to assess restrained eating. Genetic risk of obesity was assessed by calculating a polygenic risk score of 97 known BMI-related loci. RESULTS: Cross-lagged autoregressive models indicated that baseline restrained eating was unrelated to 7-year change in BMI (ß=0.00; 95% confidence interval (CI)=-0.01, 0.02). Instead, higher baseline BMI predicted greater 7-year increases in restrained eating (ß=0.08; 95% CI=0.05, 0.11). Similar results were obtained with WC. Polygenic risk score correlated positively with restrained eating and obesity indicators in both study phases, but it did not predict 7-year change in BMI or WC. However, individuals with higher genetic risk of obesity tended to gain more weight from age 20 years to baseline, and this association was more pronounced in unrestrained eaters than in restrained eaters (P=0.038 for interaction). CONCLUSIONS: Our results suggest that restrained eating is a marker for previous weight gain rather than a factor that leads to future weight gain in middle-aged adults. Genetic influences on weight gain from early to middle adulthood may vary according to restrained eating, but this finding needs to be replicated in future studies.

Longitudinal associations between depressive symptoms and body mass index in a 20-year follow-up.

OBJECTIVE: Longitudinal studies have rarely investigated changes in depressive symptoms and indicators of obesity simultaneously, although it is often proposed that the positive relationship between depression and obesity is bidirectional. The present study examined the reciprocal nature of the relationship between depressive symptoms and body mass index (BMI) in a 20-year follow-up survey. METHODS: Participants of a Finnish cohort study in 1989 at 22 years (N=1656) were followed up at ages 32 (N=1262) and 42 (N=1155) with postal questionnaires. BMI was calculated on the basis of self-reported weight and height, and depressive symptoms were assessed using the short form of the Beck Depression Inventory. Latent growth models (LGM) and cross-lagged autoregressive models were used to determine prospective associations between depressive symptoms and BMI. RESULTS: LGM analyses indicated that men with higher initial levels of depressive symptoms experienced a faster rate of increase in BMI (ß=0.20, P<0.01). Among women, change in BMI or depressive symptoms was not predicted by the other construct, but initial levels of BMI and depressive symptoms as well as their rate of change correlated positively with each other (r=0.15 and 0.37, respectively). In cross-lagged models, depressive symptoms at age 32 predicted greater BMI at 42 (ß=0.10, P<0.001) among men, whereas women with higher BMI at age 32 were more likely to have more depressive symptoms at 42 (ß=0.08, P<0.05). CONCLUSIONS: Elevated depressive symptoms predicted weight gain in men, while changes in depressive symptoms and body weight occurred concurrently in women. Tentative evidence showed that women with excess body weight were more likely to have increased symptoms of depression 10 years later. More emphasis should be placed on depressive symptoms in weight control programs as well as on reducing weight-based stigmatization and discrimination in society.

"I would like to discuss it further with an expert": a focus group study of Finnish adults' perspectives on genetic secondary findings.

Lowered costs of genomic sequencing facilitate analyzing large segments of genetic data. Ethical debate has focused on whether and what kind of incidental or secondary findings (SFs) to report, and how to obtain valid informed consent. However, people's support needs after receiving SFs have received less attention. We explored Finnish adults' perspectives on reporting genetic SFs. In this qualitative study which included four focus group discussions (N = 23) we used four vignette letters, each reporting a genetic SF predisposing to a different disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li-Fraumeni syndrome. Transcribed focus group discussions were analyzed using inductive thematic analysis. Major themes were immediate shock, dealing with worry and heightened risk, fear of being left alone to deal with SFs, disclosing to family, and identified support needs. Despite their willingness to receive SFs, participants were concerned about being left alone to deal with them. Empathetic expert support and timely access to preventive care were seen as essential to coping with shock and worry, and disclosing SFs to family. Discussion around SFs needs to concern not only which findings to report, but also how healthcare systems need to prepare for providing timely access to preventive care and support for individuals and families.