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Ischemic stroke is caused by an interruption in the flow of blood to the brain and a risk factor for death and disability. Recent genome-wide association studies have identified more than 40 common sequence variants associated with ischemic stroke. However, the results are not always the same in populations with different genetic backgrounds. In the present study, we evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions would develop unique genetic risks. We investigated the candidate genes for ischemic stroke and risk factors in a Chinese Mongolian population which has not been explored previously. A total of 167 stroke cases and 176 controls were included in the study. Genotyping was performed by amplicon sequencing. The association was detected with single nucleotide polymorphisms (SNPs) located within genes NINJ2 (rs12425791) and ALDH2 (rs2238151) as well as intergenic rs9536591 were significantly associated with ischemic stroke, of which SNP rs12425791 of the NINJ2 gene was the strongest association. ALDH2 gene encodes mitochondrial aldehyde dehydrogenase, involved in the oxidative pathway of alcohol metabolism. Sex, age, body mass index and high blood pressure might be the risk factors. The current work also demonstrated genetic heterogeneity exists between Chinese and other populations. Our study provided the new insights into the genetic basis and environmental factors of ischemic stroke in Mongolian population.

Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.