NyuWa Genome Resource : Deep Whole 1 Genome Sequencing Based Chinese 2 Population Variation Profile and Reference 3 Panel 4 Running title : NyuWa Chinese Population WGS and 5 Reference Panel

23 The lack of Chinese population specific haplotype reference panel and whole genome 24 sequencing resources has greatly hindered the genetics studies in the world’s largest 25 population. Here we presented the NyuWa genome resource based on deep (26.2X) 26 sequencing of 2,999 Chinese individuals, and constructed NyuWa reference panel of 27 5,804 haplotypes and 19.3M variants, which is the first publicly available Chinese 28 population specific reference panel with thousands of samples. Compared with other 29 panels, NyuWa reference panel reduces the Han Chinese imputation error rate by the 30 range of 30% to 51%. Population structure and imputation simulation tests supported 31 the applicability of one integrated reference panel for both northern and southern 32 Chinese. In addition, a total of 22,504 loss-of-function variants in coding and 33 noncoding genes were identified, including 11,493 novel variants. These results 34 highlight the value of NyuWa genome resource to facilitate genetics research in 35 Chinese and Asian populations. 36