Recent developments in population biobanks and the genetic architecture of complex disease

Population biobanks have radically transformed our understanding of complex disease genetics. Recent technological advances and the inclusion of diverse populations have accelerated the discovery and interpretation of variant associations. For instance, population-scale whole-genome sequencing now allows deep exploration of rare and structural variant associations, while multi-omics approaches integrating genome-wide association studies with proteomics, metabolomics, and advanced statistical methods like Mendelian randomization provide nuanced insights into genetic disease mechanisms. Additionally, cross-biobank collaborations and meta-analyses have been particularly impactful, dramatically increasing the statistical power for discovery. These efforts have identified novel genetic associations across numerous complex diseases, with significant contributions from non-European populations. However, data integration complexities, privacy concerns, and methodological limitations continue to constrain research. Here we review how recent advances have contributed to genetic discovery.