Methodological opportunities in genomic data analysis to advance health equity

Brieuc Lehmann, Leandra Bräuninger, Yoonsu Cho, Fabian Falck, Smera Jayadeva, Michael Katell, Thuy Nguyen, Antonella Perini, Sam Tallman, Maxine Mackintosh, Matt Silver, Karoline Kuchenbäcker, David Leslie, Nilanjan Chatterjee, Chris Holmes

Abstract: The causes and consequences of inequities in genomic research and medicine are complex and widespread. However, it is widely acknowledged that underrepresentation of diverse populations in human genetics research risks exacerbating existing health disparities. Efforts to improve diversity are ongoing, but an often-overlooked source of inequity is the choice of analytical methods used to process, analyse and interpret genomic data. This choice can influence all areas of genomic research, from genome-wide association studies and polygenic score development to variant prioritization and functional genomics. New statistical and machine learning techniques to understand, quantify and correct for the impact of biases in genomic data are emerging within the wider genomic research and genomic medicine ecosystems. At this crucial time point, it is important to clarify where improvements in methods and practices can, or cannot, have a role in improving equity in genomics. Here, we review existing approaches to promote equity and fairness in statistical analysis for genomics, and propose future methodological developments that are likely to yield the most impact for equity. New statistical and machine learning techniques to understand, quantify and correct for the impact of biases in genomic data are emerging. The authors review how the choice of analytical methods used to process, analyse and interpret genomic data can influence genomic research, as well as existing methodological approaches to promote equity and fairness in genomics.

External IDs:doi:10.1038/s41576-025-00839-w