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.

"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.

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.

The return of unexpected research results in a biobank study and referral to health care for heritable long QT syndrome.

BACKGROUND: In this study, we examined how biobank study participants, who were found to have long QT syndrome (LQTS), a potentially life-threatening but treatable cardiac arrhythmia condition, experienced the process of disclosure of unexpected results and referral to health care. METHODS: All 27 subjects with a LQTS mutation finding were asked to complete a questionnaire. Four participants did not uptake the re-testing and 5 others did not respond to the questionnaire. We received 17 questionnaires from 6 males and 11 females, aged 46-82; 5 of them were also willing to participate in qualitative interviews. RESULTS: Of the respondents, 16/17 had experienced the process of receiving the results as positive and useful, especially if they had had symptoms. One respondent experienced the process negatively due to concerns related to informing her children. All respondents felt that genetic results should be reported back to the participants, while 2 indicated that this should occur only in the case of treatable conditions. Respondents had informed all of their children about the genetic condition, except 2 minors. CONCLUSIONS: The respondents from a population biobank study who were informed about an unexpected genetic finding evaluated this process as mainly positive. They considered that delivering genetic information about a life-threatening but actionable condition has more beneficial than adverse consequences. The feedback policy for biobanks should include how and who is informed, advise treatment or care pathways for actionable findings, and it should also include suitable options for those who do not want to know about such findings.

The role of family factors and school achievement in the progression of adolescents to regular smoking.

This study examines whether parental smoking and single parenting were related to adolescents' school achievement and anti-smoking parental practices as well as how these factors predicted later smoking. The sample comprised 1163 Finnish students in Grades 7 through 9. Results show that at the beginning of the seventh grade, parental smoking and single parenting were related to adolescents' lower levels of school achievement. Moreover, parental smoking had moderate association with lack of house smoking rules. At the beginning of the ninth grade, these associations were strengthened and lack of house smoking rules as well as loosened perceived parental punishment for smoking was related to both parental smoking and single parenting. The likelihood of ninth grade regular smoking was greater among adolescents whose parents smoked, who had no smoking rules in their homes and had substandard school achievement. These results suggest that smoking parents and single parents had similar anti-smoking regulations for their children at the baseline but once children became older smoking parents were not able to maintain these rules as successfully as non-smoking parents and families with two parents. Motivating parents to uphold these anti-smoking regulations offers a prospective intervention opportunity.

Use of mental health services and complementary and alternative medicine in persons with common mental disorders.

OBJECTIVE: Few studies investigated the use of complementary and alternative medicine (CAM) by subjects with mental disorders. We examined the relationship between depressive, anxiety and alcohol-use disorders and their comorbidity, as well as the relationship between use of CAM and use of mental health services. METHOD: The Finnish adult (> or =30 years) population-based Health 2000 Study (n = 5987) collected information on use of CAM plus health and mental health care services. RESULTS: Generalised anxiety disorder and panic disorder were positively associated and alcohol abuse was negatively associated with use of CAM. The prevalence was highest in persons with comorbidity of anxiety and depressive disorders. The use or perceived usefulness of mental health services did not differ between CAM users and other participants. CONCLUSION: The relationship between the use of CAM and mental disorders appears to vary depending on the type of mental disorder. Use of CAM seems unrelated to the use and the perceived usefulness of mental health services.

Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing.

BACKGROUND: Identification of hereditary predisposition to cancer has limited significance if not followed by efficient cancer prevention in the family. Probands are traditionally left to inform their relatives about the increased risk, but distant relatives may remain uninformed. An approach to contacting directly at-risk persons assumed to be unaware of their increased cancer risk was taken. With cancer prevention as the ultimate goal, the study was aimed at investigating attitudes towards and psychosocial consequences of this novel strategy. METHODS: In families with hereditary non-polyposis colorectal cancer (Lynch syndrome), 286 healthy adult relatives with a 50% risk of a predisposing mutation were contacted by letter. Of these, 112 participated in counselling and predictive testing. Baseline information and information obtained 1 month after the test for 73 respondents were compared with 299 corresponding subjects, approached via the proband (family-mediated approach in our previous study) in these families. RESULTS: After the contact letter, 51% consented to the study. Of these, 92% approved of the direct contact and 33% had tried to seek information. In 34% of the mutation carriers, neoplasia was identified in the first post-test colonoscopy. Although post-test fear of cancer increased among the mutation carriers and decreased among noncarriers, almost all participants were satisfied with their decision to participate, independently of their test results, parallel to the family-mediated approach. CONCLUSION: In this large-scale study, relatives in cancer families were actively contacted to inform them of the condition and genetic counselling. Their attitudes were encouraging, and the psychosocial consequences were similar to the family-mediated approach. Our results suggest the appropriateness of direct contact as an alternative method of contact in cases of life-threatening treatable disease.

Smokers who do not want to quit--is consonant smoking related to lifestyle and socioeconomic factors?

AIMS: To examine whether consonant smokers (who say they would not like to quit) differ from dissonant smokers (who would like to quit) in other forms of health-related behaviour and socioeconomic background. METHODS: The participants included 2,709 male and 1,774 female smokers (aged 25-64 years old) from six annual population-based samples, examined between 1989 and 1994 via a mailed questionnaire. RESULTS: Consonant male smokers were more likely to be heavy drinkers, use mostly butter on bread, and to not eat vegetables. Particularly in the middle educational and income groups, consonant male smokers were more likely to be heavy drinkers. Consonant female smokers were more often heavy drinkers and more sedentary than dissonant female smokers. If a male smoker belonged to the lower income group he was more likely to be a consonant smoker. CONCLUSIONS: Consonant male smokers had more adverse health behaviours compared to dissonant smokers, but nearly half of them did not have any other adverse health behaviours. However, a negative attitude towards smoking cessation was associated with other adverse health behaviours. There were no socioeconomic differences in willingness to quit smoking among female smokers and those differences between male smoker groups were small. Factors other than motivation to quit should be targeted to diminish socioeconomic differences in smoking cessation.

Psychological consequences of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a prospective follow-up study.

Predictive genetic testing for cancer allows identification of those with the mutation (mutation positive) who should undergo cancer surveillance aiming at early detection of cancer and those without the mutation (mutation negative), whose unnecessary worry can be alleviated and who need not undergo frequent surveillance. However, there is a risk that predictive testing might have a harmful emotional impact on an individual. In the course of a predictive genetic testing protocol, we assessed general anxiety (by the State-Trait Anxiety Inventory [STAI]), fear of cancer and death, satisfaction with life and attitude to the future using a questionnaire survey in 271 individuals tested for hereditary non-polyposis colorectal cancer (HNPCC). Measurements were made before the first counseling (baseline), at the test disclosure session (STAI only) and 1 and 12 months after disclosure. Although at every measurement, the mutation-positive individuals were more afraid of cancer than those who were mutation negative, in both groups fear of cancer decreased significantly from baseline after disclosure. The mutation-positive subjects were more anxious than their counterparts immediately after the test disclosure, but the differences had disappeared at the follow-ups. In other variables, neither differences between the groups defined by mutation status nor changes with time were detected. Our findings suggest that counseling and testing relieve fear of cancer; no harmful emotional impact was detectable at the 1-year follow-up. To confirm these findings, however, the impact of testing should be studied after a longer interval. Furthermore, to evaluate the ultimate interpretation of these results, studies are needed to investigate the impact of fear of cancer on surveillance behavior among the mutation-positive subjects.

Fish consumption and depressive symptoms in the general population in Finland.

Fish contains high concentrations of omega-3 polyunsaturated fatty acids. Several studies have reported depletions of omega-3 fats among depressed patients, and a cross-national comparison has revealed a significant inverse correlation between annual prevalence of major depression and fish consumption. In a sample of 3,204 Finnish adults, depressive symptoms were estimated with the Beck Depression Inventory. A frequency question was used to measure fish consumption. Multiple logistic regression analysis was conducted to assess the association between depression and fish consumption. After the analysis adjusted for potential confounders, the likelihood of having depressive symptoms was significantly higher among infrequent fish consumers than among frequent consumers.

Depression and smoking cessation: the role of motivation and self-efficacy.

The aim of this paper is to examine whether depression, assessed using the Beck Depression Inventory, is related to smoking cessation motivation and self-efficacy. In a population sample of 1,547 Finnish men and 1,856 Finnish women, aged between 25-64 years, there were 34% male and 21% female current smokers. The current smokers had higher mean depression scores than former or never smokers. The higher depression scores were related to greater motivation to quit smoking among female smokers [OR = 1.51 (1.15-1.97)]. In addition, higher depression scores were related to lower smoking cessation self-efficacy, especially among male smokers [OR = .63 (.45-.90)]. Depression scores were not related to whether a smoker had had previous cessation attempts. Our results suggest that depression is related to lower smoking cessation self-efficacy while smokers with higher depression scores seem to be more motivated to quit smoking.

Cynical hostility, depression, and obesity: the moderating role of education and gender.

OBJECTIVE: We examined how education and gender moderate the association of obesity with cynical hostility and depression. METHOD: Body mass index (BMI), waist-to-hip ratio (WHR), years of education, cynical hostility (CynDis), depression (Beck Depression Inventory) were examined in a cross-sectional study of 1,547 men and 1,814 women, aged 25-64. RESULTS: Education moderates the positive association between cynical distrust and obesity among women in a such way that cynical distrust was not related to BMI or WHR among highly educated women. Depression had a positive association with WHR after age and education among both genders and among women with BMI. Bivariate associations between psychological factors and obesity measures were similar among men and women. DISCUSSION: The results suggest the importance of examining socioeconomic status (SES) together with psychological factors related to obesity.

Haemostatic and other cardiovascular risk factors, and socioeconomic status among middle-aged Finnish men and women.

BACKGROUND: The higher morbidity and mortality due to cardiovascular diseases (CVD) in lower social classes has been shown repeatedly in Finland. Lower socioeconomic groups also have a more adverse CVD risk factor profile. The association between socioeconomic factors and risk of CVD is only partly explained by the traditional risk factors. Fibrinogen may be of particular importance as an underlying mechanism that mediates this association. MATERIAL AND METHODS: The association of socioeconomic status (SES), as measured by years of education and family income with coronary risk factors was studied among a random population-based sample (N = 2365) of Finnish men and women aged 45 to 64. Subjects were studied in three parts of Finland; North Karelia, the Helsinki area, and South-West Finland, in connection with a larger cardiovascular monitoring programme. Years of education was divided into four categories (< or = 7, 8-9, 10-12, > or = 13) and family income into quartiles. The coronary risk factors studied were serum total cholesterol, HDL-cholesterol, triglycerides, blood pressure, prevalence of hypertension, smoking, body mass index (BMI), waist-to-hip ratio, prevalence of obesity, alcohol use and the following haemostatic factors: plasma fibrinogen, factor VII coagulant activity (factor VII:C), factor VII antigen (factor VII:Ag) and plasminogen. RESULTS: Adjusting for age and area of residence, both men and women of low SES tended either to have more adverse risk factor levels or there was no association. The only exception was proportion of heavy drinkers, which was higher among higher social class women. The inverse association of SES were especially strong and consistent with smoking among men, and with BMI in both sexes. Of the haemostatic factors studied, plasma fibrinogen was inversely associated with SES in both sexes. The association disappeared after adjustment for smoking among men but not among women. Among women, plasma factor VII:Ag was inversely associated with income. No other statistically significant associations of haemostatic factors with SES were observed. CONCLUSIONS: Low SES groups had more adverse levels of most of the CVD risk factors. Haemostatic factors appeared to be associated with SES especially among women.