A large-scale genetic study analyzing over 3,000 whole genomes from across Japan has challenged the long-standing 'dual ancestry' model of Japanese origins. Published in Science Advances, the research led by Xiaoxi Liu at RIKEN introduces a 'tripartite origins' model, identifying three distinct ancestral components: one predominant in Okinawa, another in northeastern Japan, and a third in western Japan. Genetic ties in western Japan are closest to Han Chinese, while northeastern groups show stronger affinities to ancient Korean populations and the indigenous Jōmon people.

Beyond ancestry, the study connects these genetic lineages to regional health patterns. Two hereditary BRCA mutations—BRCA1 in the northeast and BRCA2 in the west—suggest separate continental origins for each. The dataset, named JEWEL, uncovered nearly 9,800 previously unrecorded loss-of-function variants, including links to Dubin-Johnson syndrome and cardiovascular conditions.

The research also found that Neanderthal and Denisovan DNA segments influence modern disease risk. A Denisovan-derived segment near NKX6-1 and a Neanderthal segment near GLP1R—both genes involved in diabetes—are associated with type 2 diabetes, with implications for how treatments like semaglutide may vary across populations. Signals of recent natural selection were detected in genes related to alcohol metabolism and immune function, though weaker in Okinawa, suggesting regional evolutionary pressures.