A comprehensive DNA methylation atlas for the Chinese population through nanopore long-read sequencing of 106 individuals

Abstract

DNA methylation constitutes the primary epigenetic language mediating organismal phenotypic plasticity. Establishing a cohort-level genomic methylation landscape featuring wide geographical diversity is fundamental for dissecting its genetic and environmental attributes. Leveraging nanopore sequencings strength in genome-methylome co-sequencing, we generated a whole-genome, haplotype-resolved methylation atlas for 106 individuals from 19 provinces across China. The atlas identified 27,609,354 CpG sites genome-wide, with notably more informed gene proximal regions and CpG islands compared to whole-genome bisulfite sequencing. Detailed analyses revealed genomic structural variants as a pervasive covariate of DNA methylation, with a remarkable 2-fold compensation effect found in genome-wide heterozygous deletions. On the other hand, habitat altitude is found to be a strong environmental determinant of DNA methylation. We established a quantitative relationship between altitude and methylation states and identified a gene set strictly responsive to altitude differences, revealing epigenetically regulated genes such as PRDM16, EPHB2 and WNT7A. The methylation atlas provides a reference resource to facilitate further explorations into human epigenetics.