Leveraging large-scale biobanks for genetic discovery and better public health

Biobank studies, connecting genetics with health and sociodemographic information for thousands of individuals, have demonstrated to hold exceptional potential for epidemiological and genetic discoveries, yielding thousands of phenotypic and genetic associations that pose a solid base to delve further into the determinants of health and disease. This thesis consists of four distinct studies, two investigating the factors leading people to participate in biobank studies and how these can affect the interpretation of genetic results, and two showcasing the potential of large-scale biobanks in unveiling new insights into extremely relevant traits, such as medication adherence and COVID-19. In our first study, we identify a novel way in which individuals engage with research studies, which sees males and females participate in a differential manner. We showed the consequences of this mechanism on genetic analyses and advice on how to account for it and improve future representativeness of genetic data collection. In our second study, we observe how study participants tend to choose non-response options in surveys in a systematic way and how this behavior has a genetic basis. We explore further the determinants of this phenomenon and strongly recommend this behavior be accounted for in all survey-based research. In our third study, we use nationwide and biobank data to draw a comprehensive picture of the factors affecting drug adherence across five medications. We observe how genetics show limited effect on it while measures of social deprivation and behavioral factors associated with participation play a major role. We conclude that socio-economically disadvantaged groups will likely benefit from targeted interventions to improve drug adherence. Finally, in our fourth study, we showcase how biobanks can globally and effectively come together to provide a better understanding of the emerging COVID-19 disease. We identify distinct genetic factors affecting COVID-19 susceptibility and severity and reiterate the value of collaborative science. Collectively, our findings offer important lessons on how large-scale biobanks can be leveraged to advance the understating of human health and disease and, ultimately, enhance population health.