Dissecting Population Substructure in India via Correlation Optimization of Genetics and Geodemographics

India represents an intricate tapestry of population sub-structure shaped by geography, language, culture and social stratification operating in concert [1–3]. To date, no study has attempted to model and evaluate how these evolutionary forces have interacted to shape the patterns of genetic diversity within India. Geography has been shown to closely correlate with genetic structure in other parts of the world [4,5]. However, the strict endogamy imposed by the Indian caste system, and the large number of spoken languages add further levels of complexity. We merged all publicly available data from the Indian subcontinent into a dataset of 835 individuals across 48,373 SNPs from 84 well-defined groups [2, 6–9]. Bringing together geography, sociolinguistics and genetics, we developed COGG (Correlation Optimization of Genetics and Geodemographics) in order to build a model that optimally explains the observed population genetic sub-structure. We find that shared language rather than geography or social structure has been the most powerful force in creating paths of gene flow within India. Further investigating the origins of Indian substructure, we create population genetic networks across Eurasia. We observe two major corridors towards mainland India; one through the Northwestern and another through the Northeastern frontier with the Uygur population acting as a bridge across the two routes. Importantly, network, ADMIXTURE analysis and f3 statistics support a far northern path connecting Europe to Siberia and gene flow from Siberia and Mongolia towards Central Asia and India. The genetic structure of human populations reflects gene flow around and through geographic, linguistic, cultural, and social barriers. We set out to explore how the complex interplay of these factors may shape the patterns of genetic variation focusing on India, a country of intriguing levels of population structure complexity. The caste system in India has been documented since 1500-1000 BC and imposes strict rules of endogamy over the past several thousands of years. Social stratification within India may be summarised into the so-called Forward Castes and the Backward Castes [10], while 8.2% of the total population belongs to Scheduled Tribes and represents minorities that lie outside the caste system, still largely based on hunting, gathering and unorganized agriculture, with no written form of language [11]. Furthermore, there are 22 official languages within India, also following a distinctive geographic spread. The Dravidian (DR) speaking groups inhabit southern India, Indo-European (IE) speakers inhabit primarily northern India (but also parts of west and east India as well) and Tibeto-Burman (TB) speakers are mostly confined to northeastern India. The numerically small group of Austro-Asiatic (AA) speakers, who are exclusively tribal and are thought to be the original inhabitants of mainland India, inhabit fragmented geographical areas of eastern and central India. Previous studies have