HiLand Resource: A Comprehensive Database of Highland Human Populations.

Abstract

Over 80 million people worldwide live at high altitudes (> 2500 m), where numerous studies have documented the remarkable biological adaptations of highland populations to these extreme environments. However, current resources for accessing and analyzing highlander-specific data remain limited. To address this gap, we present the HiLand Resource (HLR), a comprehensive database that integrates phenomic, genomic, and genetic association data from 29,977 highlanders across three major high-altitude regions: the Qinghai-Xizang Plateau, the Andean Plateau, and the Ethiopian Plateau. HLR offers six key functions: (1) visualization of phenotypic pattern among Qinghai-Xizang highlanders across different altitudes, as well as comparison between highlanders and lowlanders, and between sexes; (2) an interactive interface to explore genomic diversity, population structure, ancestral composition, and signatures of natural selection of high-altitude populations; (3) access to a comprehensive catalog of genome-wide variants and genes identified in highlanders; (4) a genome browser built on a high-quality Tibetan genome assembly; (5) a curated collection of genotype-phenotype associations derived from genome-wide association studies (GWAS) in highland populations; and (6) an online, user-friendly tool for genotype imputation using a highland-specific reference panel. Collectively, HLR provides a novel and in-depth resource for understanding the biological features of high-altitude human populations. It holds significant potential for advancing research on human adaptation to hypoxic environments and improving medical studies focused on highland communities. The HLR database is freely available at: https://ngdc.cncb.ac.cn/hiland/.