Global Public Perceptions of Genomic Data Sharing: What Shapes the Willingness to Donate DNA and Health Data?

Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this.

Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome.

PURPOSE: Universal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database. METHODS: All patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database. RESULTS: IHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS. CONCLUSION: Universal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm.

Return of genomic results does not motivate intent to participate in research for all: Perspectives across 22 countries.

PURPOSE: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. METHODS: We analyzed the "Your DNA, Your Say" online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. RESULTS: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. CONCLUSION: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants' preferences for return of genomic results globally should be considered.

[Increased use of genetic health care in Iceland 2012-2017].

INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%.

Molecular genetics of inherited retinal degenerations in Icelandic patients.

The study objective was to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, a small nation of 364.000 and a genetic isolate. Benefits include delineating novel pathogenic genetic variants and defining genetically homogenous patients as potential investigative molecular therapy candidates. The study sample comprised patients with IRD in Iceland ascertained through national centralized genetic and ophthalmological services at Landspitali, a national social support institute, and the Icelandic patient association. Information on patients' disease, syndrome, and genetic testing was collected in a clinical registry. Variants were reevaluated according to ACMG/AMP guidelines. Overall, 140 IRD patients were identified (point prevalence of 1/2.600), of which 70 patients had a genetic evaluation where two-thirds had an identified genetic cause. Thirteen disease genes were found in patients with retinitis pigmentosa, with the RLBP1 gene most common (n = 4). The c.1073 + 5G > A variant in the PRPF31 gene was homozygous in two RP patients. All tested patients with X-linked retinoschisis (XLRS) had the same possibly unique RS1 pathogenic variant, c.441G > A (p.Trp147X). Pathologic variants and genes for IRDs in Iceland did not resemble those described in ancestral North-Western European nations. Four variants were reclassified as likely pathogenic. One novel pathogenic variant defined a genetically homogenous XLRS patient group.

Comparing prenatal screening experiences of Icelandic women who received false-positive and true-negative first-trimester combined screening results in Iceland in 2012-2016.

First-trimester combined screening (FTS) has been offered to all pregnant women in Iceland since 2003. Individuals with high-risk FTS results are offered an invasive test option with a ≤1% risk of fetal loss. This study gives insight into the prenatal screening and diagnosis experiences and preferences of 101 women who underwent FTS in Iceland in the years 2012-2016, comparing the experience of those who received false-positive FTS results to those who received true-negative results. Retrospective patient-reported anxiety levels at the time of receiving FTS results were significantly higher in those who received false-positive results compared to those who received true-negative results. For a subset of these participants, the anxiety lasted through pregnancy, and for a smaller subset, it lasted even longer. Non-invasive prenatal testing (NIPT) is currently not offered in Iceland, aside from the rare exceptional case. Given the extremely low false-positive rates of NIPT, we believe NIPT is worth considering as Iceland's standard first-tier screening method for trisomy 13, 18, and 21. We believe the findings of this study are beneficial not only for Iceland but also for other countries where FTS is the first-tier prenatal screening method or the only offered test. Additionally, only 21% of participants in our study reported that they had heard of NIPT, which emphasizes the need for comprehensive NIPT pretest information to be available prior to its uptake to ensure informed and autonomous decision-making.

Correction: The Gen-Equip Project: evaluation and impact of genetics e-learning resources for primary care in six European languages.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly.

The Gen-Equip Project: evaluation and impact of genetics e-learning resources for primary care in six European languages.

PURPOSE: Genetic advances mean patients at risk of genetic conditions can be helped through testing, clinical screening, and preventive treatment, but they must first be identified to benefit. Ensuring quality of genetic care for patients requires genetic expertise in all health services, including primary care. To address an educational shortfall, a series of e-learning resources was developed in six languages to equip primary care professionals with genetic skills relevant for practice. The purpose of the study was to evaluate these resources using Kirkpatrick's framework for educational outcomes. METHODS: Mixed methods (qualitative and quantitative) were used over four phases of the study. RESULTS: A high level of satisfaction with the resources was reported. Knowledge and skills improved significantly after using the education material. Participants reported changes in confidence and practice behavior, including family history taking, seeking advice from specialists and referring patients. The resources helped users to learn how to explain genetics. Many visited the resources repeatedly and some used them to educate colleagues or students. CONCLUSION: Gen-Equip modules are effective in improving genetic knowledge, skills, and attitudes for primary care professionals. They provide both continuing professional development and just-in-time learning for a potentially large global audience at a practical level.

Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers.

BACKGROUND: The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers. METHODS: We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012. RESULTS: Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03). CONCLUSIONS: Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics' database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder.