{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:05:06Z","timestamp":1781701506139,"version":"3.54.5"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over 80 million people worldwide live at high altitudes (&amp;gt; 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 23,336 highlanders across three major high-altitude regions: the Qinghai-Tibet Plateau, the Andean Plateau, and the Ethiopian Plateau. HLR offers six key functions: (1) visualization of phenotypic patterns among highlanders from the Qinghai-Tibet Plateau 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\u2013phenotype associations derived from genome-wide association studies (GWASs) 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\/.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzaf083","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T19:27:43Z","timestamp":1758310063000},"source":"Crossref","is-referenced-by-count":1,"title":["HiLand Resource: A Comprehensive Database of Highland Human Populations"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4141-4932","authenticated-orcid":false,"given":"Weijie","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2984-9085","authenticated-orcid":false,"given":"Xiaoning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-3625","authenticated-orcid":false,"given":"Yanling","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2868-4888","authenticated-orcid":false,"given":"Yibo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-4411","authenticated-orcid":false,"given":"Bixia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-5306","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4065-5763","authenticated-orcid":false,"given":"Kai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4396-8287","authenticated-orcid":false,"given":"Wenming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-9014","authenticated-orcid":false,"given":"Bing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3324-3239","authenticated-orcid":false,"given":"Yaoxi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"2026061708371218400_qzaf083-B1","doi-asserted-by":"crossref","first-page":"e2102463118","DOI":"10.1073\/pnas.2102463118","article-title":"Global and country-level estimates of human population at high altitude","volume":"118","author":"Tremblay","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061708371218400_qzaf083-B2","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1101\/gad.250167.114","article-title":"Human high-altitude adaptation: forward genetics meets the HIF pathway","volume":"28","author":"Bigham","year":"2014","journal-title":"Genes Dev"},{"key":"2026061708371218400_qzaf083-B3","first-page":"388","article-title":"King of the mountains: Tibetan and Sherpa physiological adaptations for life at high altitude","volume":"29","author":"Gilbert-Kawai","year":"2014","journal-title":"Physiology (Bethesda)"},{"key":"2026061708371218400_qzaf083-B4","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/152702901750265341","article-title":"Human genetic adaptation to high altitude","volume":"2","author":"Moore","year":"2001","journal-title":"High Alt Med Biol"},{"key":"2026061708371218400_qzaf083-B5","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1093\/molbev\/msab064","article-title":"High-altitude adaptation: mechanistic insights from integrated genomics and physiology","volume":"38","author":"Storz","year":"2021","journal-title":"Mol Biol Evol"},{"key":"2026061708371218400_qzaf083-B6","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/nsr\/nwz160","article-title":"De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation","volume":"7","author":"Ouzhuluobu","year":"2020","journal-title":"Natl Sci Rev"},{"key":"2026061708371218400_qzaf083-B7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13059-023-02912-1","article-title":"Large-scale genome sequencing redefines the genetic footprints of high-altitude adaptation in Tibetans","volume":"24","author":"Zheng","year":"2023","journal-title":"Genome Biol"},{"key":"2026061708371218400_qzaf083-B8","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1073\/pnas.1617042114","article-title":"Genetic signatures of high-altitude adaptation in Tibetans","volume":"114","author":"Yang","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061708371218400_qzaf083-B9","doi-asserted-by":"crossref","first-page":"4037","DOI":"10.1016\/j.cub.2023.08.021","article-title":"Polygenic adaptation leads to a higher reproductive fitness of native Tibetans at high altitude","volume":"33","author":"He","year":"2023","journal-title":"Curr Biol"},{"key":"2026061708371218400_qzaf083-B10","doi-asserted-by":"crossref","first-page":"107677","DOI":"10.1016\/j.isci.2023.107677","article-title":"Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans","volume":"26","author":"He","year":"2023","journal-title":"iScience"},{"key":"2026061708371218400_qzaf083-B11","doi-asserted-by":"crossref","first-page":"D984","DOI":"10.1093\/nar\/gkx1032","article-title":"PGG.Population: a database for understanding the genomic diversity and genetic ancestry of human populations","volume":"46","author":"Zhang","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2026061708371218400_qzaf083-B12","doi-asserted-by":"crossref","first-page":"D971","DOI":"10.1093\/nar\/gkz829","article-title":"PGG.Han: the Han Chinese genome database and analysis platform","volume":"48","author":"Gao","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2026061708371218400_qzaf083-B13","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1080\/02713683.2017.1408127","article-title":"Central corneal thickness of healthy lowlanders at high altitude: a systematic review and meta-analysis","volume":"43","author":"Liu","year":"2018","journal-title":"Curr Eye Res"},{"key":"2026061708371218400_qzaf083-B14","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/ICO.0b013e31802e63c8","article-title":"Corneal thickness at high altitude","volume":"26","author":"Morris","year":"2007","journal-title":"Cornea"},{"key":"2026061708371218400_qzaf083-B15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1089\/ham.2006.7.193","article-title":"High altitude adaptation in Tibetans","volume":"7","author":"Wu","year":"2006","journal-title":"High Alt Med Biol"},{"key":"2026061708371218400_qzaf083-B16","first-page":"201","article-title":"Tibetan and Andean patterns of adaptation to high-altitude hypoxia","volume":"72","author":"Beall","year":"2000","journal-title":"Hum Biol"},{"key":"2026061708371218400_qzaf083-B17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1093\/nsr\/nwz108","article-title":"Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders","volume":"6","author":"Deng","year":"2019","journal-title":"Natl Sci Rev"},{"key":"2026061708371218400_qzaf083-B18","doi-asserted-by":"crossref","first-page":"24006","DOI":"10.1073\/pnas.1906171116","article-title":"Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude","volume":"116","author":"Brutsaert","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061708371218400_qzaf083-B19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ajhg.2012.05.015","article-title":"Ethiopian genetic diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool","volume":"91","author":"Pagani","year":"2012","journal-title":"Am J Hum Genet"},{"key":"2026061708371218400_qzaf083-B20","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1016\/j.cell.2024.07.009","article-title":"The need to diversify genomic studies: insights from Andean highlanders and Amazonians","volume":"187","author":"Alvim","year":"2024","journal-title":"Cell"},{"key":"2026061708371218400_qzaf083-B21","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-023-01394-y","article-title":"Including multiracial individuals is crucial for race, ethnicity and ancestry frameworks in genetics and genomics","volume":"55","author":"Martschenko","year":"2023","journal-title":"Nat Genet"},{"key":"2026061708371218400_qzaf083-B22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1126\/science.adq7784","article-title":"Genomic diversity improves disease discovery for all","volume":"385","author":"Williamson","year":"2024","journal-title":"Science"},{"key":"2026061708371218400_qzaf083-B23","doi-asserted-by":"crossref","first-page":"e1007650","DOI":"10.1371\/journal.pgen.1007650","article-title":"Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal","volume":"14","author":"Jeong","year":"2018","journal-title":"PLoS Genet"},{"key":"2026061708371218400_qzaf083-B24","doi-asserted-by":"crossref","first-page":"6134","DOI":"10.1073\/pnas.1422759112","article-title":"Genetic differences and aberrant methylation in the apelin system predict the risk of high-altitude pulmonary edema","volume":"112","author":"Mishra","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061708371218400_qzaf083-B25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1089\/ham.2015.0065","article-title":"A preliminary genome-wide association study of acute mountain sickness susceptibility in a group of nepalese pilgrims ascending to 4380 m","volume":"16","author":"MacInnis","year":"2015","journal-title":"High Alt Med Biol"},{"key":"2026061708371218400_qzaf083-B26","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1080\/07391102.2019.1711190","article-title":"Structural and functional alterations of nitric oxide synthase 3 due to missense variants associate with high-altitude pulmonary edema through dynamic study","volume":"39","author":"Kanipakam","year":"2021","journal-title":"J Biomol Struct Dyn"},{"key":"2026061708371218400_qzaf083-B27","doi-asserted-by":"crossref","first-page":"e0269671","DOI":"10.1371\/journal.pone.0269671","article-title":"Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population","volume":"17","author":"Bhandari","year":"2022","journal-title":"PLoS One"},{"key":"2026061708371218400_qzaf083-B28","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.ajhg.2022.04.014","article-title":"Clotting factor genes are associated with preeclampsia in high-altitude pregnant women in the Peruvian Andes","volume":"109","author":"Nieves-Colon","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2026061708371218400_qzaf083-B29","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3389\/fgene.2019.00690","article-title":"The genetic architecture of chronic mountain sickness in Peru","volume":"10","author":"Gazal","year":"2019","journal-title":"Front Genet"},{"key":"2026061708371218400_qzaf083-B30","doi-asserted-by":"crossref","first-page":"e1003110","DOI":"10.1371\/journal.pgen.1003110","article-title":"The genetic architecture of adaptations to high altitude in Ethiopia","volume":"8","author":"Alkorta-Aranburu","year":"2012","journal-title":"PLoS Genet"},{"key":"2026061708371218400_qzaf083-B31","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/j.cell.2022.08.004","article-title":"High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios","volume":"185","author":"Byrska-Bishop","year":"2022","journal-title":"Cell"},{"key":"2026061708371218400_qzaf083-B32","doi-asserted-by":"crossref","DOI":"10.1126\/science.aay5012","article-title":"Insights into human genetic variation and population history from 929 diverse genomes","volume":"367","author":"Bergstr\u00f6m","year":"2020","journal-title":"Science"},{"key":"2026061708371218400_qzaf083-B33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"2026061708371218400_qzaf083-B34","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1371\/journal.pgen.0020190","article-title":"Population structure and eigenanalysis","volume":"2","author":"Patterson","year":"2006","journal-title":"PLoS Genet"},{"key":"2026061708371218400_qzaf083-B35","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet"},{"key":"2026061708371218400_qzaf083-B36","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/nprot.2010.116","article-title":"Data quality control in genetic case-control association studies","volume":"5","author":"Anderson","year":"2010","journal-title":"Nat Protoc"},{"key":"2026061708371218400_qzaf083-B37","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/ng.2310","article-title":"Genome-wide efficient mixed-model analysis for association studies","volume":"44","author":"Zhou","year":"2012","journal-title":"Nat Genet"},{"key":"2026061708371218400_qzaf083-B38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13059-023-02914-z","article-title":"JBrowse 2: a modular genome browser with views of synteny and structural variation","volume":"24","author":"Diesh","year":"2023","journal-title":"Genome Biol"},{"key":"2026061708371218400_qzaf083-B39","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.gpb.2022.12.004","article-title":"Database Commons: a catalog of worldwide biological databases","volume":"21","author":"Ma","year":"2023","journal-title":"Genomics Proteomics Bioinformatics"}],"container-title":["Genomics, Proteomics &amp; Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article-pdf\/doi\/10.1093\/gpbjnl\/qzaf083\/64263405\/qzaf083.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/23\/5\/qzaf083\/64263405\/qzaf083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/article-pdf\/23\/5\/qzaf083\/64263405\/qzaf083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:37:23Z","timestamp":1781699843000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gpb\/article\/doi\/10.1093\/gpbjnl\/qzaf083\/8253738"}},"subtitle":[],"editor":[{"given":"Jingyuan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,14]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10,28]]}},"URL":"https:\/\/doi.org\/10.1093\/gpbjnl\/qzaf083","relation":{},"ISSN":["1672-0229","2210-3244"],"issn-type":[{"value":"1672-0229","type":"print"},{"value":"2210-3244","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,9,14]]},"article-number":"qzaf083"}}