This paper explores the historical and social context of population genetic research conducted in India by focusing on a study by Reich et al which aimed to reconstruct Indian population history. The paper addresses two themes. First, it considers the agendas and modes of thinking about Indian populations and the caste system on which this study appears to be based. Second, it reflects on the medical implications of this study as they were presented in Reich et al's findings. I suggest that while genetic mapping of Indian populations appears to have inherited many of the problems characteristic of population genetic research conducted in the USA and globally, the specificity of this research in India involves a peculiar interplay of the postcolonial pursuit of genomic sovereignty, desire by the Indian state to become a player in the global realm of biotechnology, and age-old discourses naturalising caste and regional differences. My argument is that, although the study has offered conceptual space for a wide range of interpretations, it has a strong potential not just for naturalising caste and regional differences in India, but also for pathologising them without necessarily bringing tangible healthcare benefits in the foreseeable future.