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

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. 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. A total of 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' 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]). 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.