What People Want to Know About Their Genes: A Critical Review of the Literature on Large-Scale Genome Sequencing Studies

Abstract

From a public health perspective, the “All of Us” study provides an opportunity to isolate targeted and cost-effective prevention and early-detection strategies. Identifying motivations for participation in large-scale genomic sequencing (LSGS) studies, and motivations and preferences to receive results will help determine effective strategies for “All of Us” study implementation. This paper offers a critical review of the literature regarding LSGS for adult onset hereditary conditions where results could indicate an increased risk to develop disease. The purpose of this review is to synthesize studies which explored peoples’ motivations for participating in LSGS studies, and their desire to receive different types of genetic results. Participants were primarily motivated by altruism, desire to know more about their health, and curiosity. When asked about hypothetically receiving results, most participants in hypothetical studies wanted all results except those which were uncertain (i.e., a variant of uncertain significance (VUS)). However, participants in studies where results were returned preferred to receive only results for which an intervention was available, but also wanted VUS. Concerns about peoples’ understanding of results and possible psychosocial implications are noted. Most studies examined populations classified as “early adopters,” therefore, additional research on motivations and expectations among the general public, minority, and underserved populations is needed.

Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing

“…This result is similar to that obtained by Hitch et al (2014), who found that 63% of participants wanted to receive all possible results from ES. In general, the finding that the majority of people undergoing ES/GS report wanting to receive all possible results is in line with previous studies, mainly carried out in North America (Scherr et al, 2018;Shahmirzadi et al, 2014;Wynn et al, 2017), which suggests that such preferences are not influenced by potential country-based socio-cultural differences. The highest proportion of participants wanting to know all possible test results was found among those screened for a recessive condition (88.9%), that is individuals without a specific personal/family history of disease, consistent with results from studies on healthy adult populations (Murphy et al, 2008;Roberts et al, 2018;Scherr et al, 2018).…”

“…Recommendations in favor of disclosing 'clinically actionable' genetic alterations (Ploug & Holm, 2017) have been criticized for not taking into account patient preferences ('patient actionable' genes; Mackley et al, 2017;Scherr et al, 2018). Nonetheless, most of the studies exploring preferences about the disclosure of SFs focused on healthy adults or participants in genetic research (Hitch et al, 2014;Roberts et al, 2018), while very limited evidence exists on attitudes of actual clinical users, that is, patients undergoing clinical genetic testing (Mackley et al, 2017).…”

Preferences for Updates on General Research Results: A Survey of Participants in Genomic Research from Two Institutions

“…Our study population, therefore, may not represent the general public with respect to their motivations to participate in research. For example, personal/family benefit is a common motivator to participate in large-scale genomic sequencing studies [ 27 ]. For our selected studies, there were not opportunities for personal/family benefit; thus, this was unlikely to be a motivator.…”

Understanding polygenic models, their development and the potential application of polygenic scores in healthcare

“… 22 46 67–70 This is an ongoing challenge in genomics as most GWAS, from which most PGS are being developed, have been conducted in European-Caucasian populations. 71 Efforts to improve representation are underway 72 and there are attempts to reweight/adjust scores when applied to different population groups which are showing some potential but need further research. 47 Others have demonstrated that models developed in more diverse population groups have improved performance when applied to external data sets in different populations.…”