Perceived risk of type 2 diabetes: Using linked genomic, clinical and questionnaire data to understand the potential use of genetic risk tools in British South Asians

Background Despite growing interest surrounding the integration of genetic risk tools such as polygenic risk scores (PRSs) into routine care for early disease identification and management, major questions remain about whether and how these tools are to be implemented at-scale. Many interventions have explored their use in encouraging the adoption of preventative health behaviours—yet existing evidence remains undetermined, limited by the focus on White European populations. The present study used structural equation modelling to explore genetic risk perceptions surrounding type 2 diabetes (T2D) in a sample of British Bangladeshi and British Pakistani volunteers—combining questionnaire data alongside genomic and clinical information to identify the characteristics of individuals who are likely to act on genetic risk information. Methods and findings We conducted this study with volunteers enrolled in Genes & Health—a large-scale (n > 60,000) study in the UK recruiting British Bangladeshi and British Pakistani volunteers from community and NHS settings. Eligible participants between the ages of 16 to 59 years were invited to complete a 15-minute questionnaire containing measures of genetic risk perceptions surrounding T2D, as well as intention to adopt health behaviours and that can prevent or delay T2D. Questionnaire responses were then integrated with participants’ genomic and clinical data available at Genes & Health to construct a model—characterising their mediating relationships in informing participants’ intention. 626 participants responded to the questionnaire (response rate = 17%, 37.70% aged 46 to 59 years, 62.62% female). Being between the ages of 46 to 59 years (β = 0.52, 95% CI [0.26, 0.79], p < 0.05), having greater self-reported perceived control over health (β = 0.41, 95% CI [0.26, 0.56], p < 0.05) and interest in genetic testing (β = 0.62, 95% CI [0.46, 0.78], p < 0.05) all had direct positive effects on participants’ intention. Household income showed an indirect effect on intention, mediated by interest in genetic testing, β = 0.24, 95% CI [0.12, 0.37]. Self-identified ethnicity also demonstrated indirect effects on intention via two mediating pathways—both involving participants’ actual T2D PRSs and self-reported family history of T2D (β = 0.03, 95% CI [0.02, 0.05] and β = 0.002, 95% CI [0.001, 0.01]). Conclusions Our results showed that older age, greater perceived control over health and interest in genetic testing are all predictive of participants’ likelihood of adopting preventative heath behaviours in response to genetic risk information about T2D. We also found evidence pointing to the roles that wider socio-demographic, clinical and familial variables can play in informing and mediating genetic risk perceptions. These findings should raise awareness about potential challenges to the equitable delivery and management of genetic risk tools—and strengthen calls for wider family- and system-level approaches that can help address potential health inequalities, as efforts surrounding the large-scale implementation of genomics into existing health systems continue to grow. Why was this study done? What did the researchers do and find? What do these findings mean? ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was made possible by funding from the Wellcome Trust for JHL through the doctoral training programme Health Data in Practice: Human-centred Science (Reference: 218584/Z/19/Z). Genes & Health has recently been core-funded by Wellcome (WT102627, WT210561), the Medical Research Council (UK) (M009017, MR/X009777/1, MR/X009920/1), Higher Education Funding Council for England Catalyst, Barts Charity (845/1796), Health Data Research UK (for London substantive site), and research delivery support from the NHS National Institute for Health Research Clinical Research Network (North Thames). Genes & Health has recently been funded by Alnylam Pharmaceuticals, Genomics PLC; and a Life Sciences Industry Consortium of Astra Zeneca PLC, Bristol-Myers Squibb Company, GlaxoSmithKline Research and Development Limited, Maze Therapeutics Inc, Merck Sharp & Dohme LLC, Novo Nordisk A/S, Pfizer Inc, Takeda Development Centre Americas Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Genes & Health operates under ethical approval from the London South East National Research Ethics Committee and Health Research Authority (Reference: 14/LO/1240), with Queen Mary University of London as Sponsor. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.