Evidence map›Paper›PMID 42086051›Full record

ArticleAmerican journal of human genetics2026

Signatures of pathogen-driven selection and Austronesian gene flow of Papua New Guinea HLA alleles.

Neus Font-Porterias, Neda Nemat-Gorgani, Katherine M Kichula, Dana R Al-Hindi, Genelle F Harrison, Sudan Tao, Faming Zhu, Gonzalo Montero-Martin, Marcelo A Fernández-Viña, Lisbeth A Guethlein and 8 more

Abstract read
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In one paragraph

Article in American journal of human genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Neus Font-PorteriasDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Neda Nemat-GorganiDepartment of Structural Biology and Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Katherine M KichulaDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Dana R Al-HindiDepartment of Anthropology and the Genome Center, University of California, Davis, Davis, CA 95616, USA.
Genelle F HarrisonDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Sudan TaoDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Blood Center of Zhejiang Province, Hangzhou 310052, Zhejiang, China.
Faming ZhuBlood Center of Zhejiang Province, Hangzhou 310052, Zhejiang, China.
Gonzalo Montero-MartinStanford Blood Center, Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Marcelo A Fernández-ViñaStanford Blood Center, Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Lisbeth A GuethleinDepartment of Structural Biology and Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Peter ParhamDepartment of Structural Biology and Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
Stephen J OppenheimerInstitute of Social and Cultural Anthropology, School of Anthropology and Museum Ethnography, University of Oxford, Oxford OX3 7LF, UK.
Alexander G IoannidisGenomics Institute, UC Santa Cruz, Santa Cruz, CA 95064, USA.
Andrés Moreno-EstradaAging Research Center, Cinvestav Sede Sur, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico.
William PomatPapua New Guinea Institute of Medical Research, Post Office Box 60, Goroka, Papua New Guinea.
Alexander J MentzerWellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK.
Brenna M HennDepartment of Anthropology and the Genome Center, University of California, Davis, Davis, CA 95616, USA.
Paul J NormanDepartment of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: paul.norman@ucdenver.edu.

Funding

Evolution and Function of Immunogenetic Diversity across the Eastern HemisphereR01AI151549 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Paul John Norman · 2022 to 2026
$3.9M
Supplement: Improving Inference of Genetic Architecture and Selection with African GenomesR35GM133531 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HENN, BRENNA M · 2019 to 2023
$2.3M
NIAID NIH HHS R01 AI151549NIGMS NIH HHS R35 GM133531
6 · The paper itself

Abstract

Human leukocyte antigen (HLA) class I and II are cell surface proteins that display peptide antigens to immune cells, thereby mediating detection of infected cells and production of antibodies. Pathogen exposure and demographic events, including local adaptation and admixture, have driven and maintained exceptional polymorphism of HLA genes across human populations. Papua New Guinea has a complex demography, with geographically distinct populations in the highlands and lowlands and exceptional linguistic heterogeneity throughout the island. The lowland populations retain signatures of Austronesian expansion ∼3,000 years ago. Papua New Guinea populations are also differentially exposed to endemic malarial pathogens, with a greater burden in the lowlands. We analyzed genome-wide autosomal SNP data together with HLA allele sequences, linguistic, and geographical data from 337 Papuans. We find the substructure of HLA alleles to be highly correlated with altitude in Papua New Guinea, a signal that is distinct from the rest of the genome. In addition, specific HLA-B and HLA-DP alleles in lowland groups have a greater number of homozygous genotypes than expected under neutrality. Some of these HLA alleles are of Austronesian genetic ancestry. We find that the HLA-binding repertoires at candidate loci are significantly enriched for antigenic P. falciparum-derived peptides. Together, these results indicate that pathogen-driven selective pressures correlate with the observed HLA genetic substructure in Papua New Guinea, highlighting the critical importance of characterizing highly complex HLA variation in understanding differences in disease susceptibility across diverse human groups.

Indexed as

Gene FlowHLA AntigensSelection, GeneticAllelesGenetics, PopulationHumansPapua New GuineaPolymorphism, Single NucleotideHLA Antigensgenetic ancestrygenetic substructuregenome-wide autosomal dataHLA diversityhuman population geneticsimmunogeneticsPapua New Guineapathogen-driven selective pressuresPlasmodium falciparum

Identifiers

PMID42086051
PMCPMC13277694

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.