Mitochondrial Genome Variants and Nuclear Mitochondrial DNA Segments in 7331 Individuals from NyuWa and 1KGP

Dysfunctional mitochondria are implicated in various diseases, but comprehensive characterization of mitochondrial DNA (mtDNA) in the Chinese population remains limited. Here, we conducted a systematic analysis of mtDNA from 7331 samples, comprising 4129 Chinese samples from the NyuWa cohort and 3202 samples from the 1000 Genomes Project (1KGP). We identified 7216 high-quality mtDNA variants, which classified 7266 samples into 22 macro-haplogroups, and detected 1466 nuclear mitochondrial DNA segments (NUMTs). Among these, 88 mtDNA variants and 642 NUMTs were specific to NyuWa. Genome-wide association analyses revealed significant correlations between 12 mtDNA variants and 199 nuclear DNA (nDNA) variants. Our findings demonstrated that all individuals in both NyuWa and 1KGP harbored common NUMTs, while one-fifth possessed ultra-rare NUMTs that tended to insert into nuclear gene regions. Notably, rare NUMTs in the NyuWa cohort showed significant enrichment of nuclear breakpoints in long interspersed nuclear elements (LINEs) compared to 1KGP. Overall, this study provides the first comprehensive profile of NUMTs in the Chinese population and establishes the most extensive resource of Chinese mtDNA variants and NUMTs to date based on high-depth whole-genome sequencing, providing valuable reference resources for genetic research on mtDNA-related diseases.