Sequence-based HLA genotyping identifies six candidate alleles associated with human longevity in Germans
*Correspondence to:
Almut Nebel,Institute of Clinical Molecular Biology, Kiel University, Kiel, Schleswig-Holstein 24105, Germany.
E-mail: a.nebel@mucosa.de
Geromedicine. 2026;2:202619. 10.70401/Geromedicine.2026.0039
Received: March 25, 2026Accepted: September 11, 2026Published: September 11, 2026
This manuscript is made available in its unedited form to allow early access to the
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Abstract
Aims: Human leukocyte antigen (HLA) polymorphism influences immunity by balancing protection against pathogens with the preservation of self-tolerance. This balance has been proposed to affect longevity, as associations with HLA variants have been identified. However, studies in this field have reported inconsistent findings due to small sample sizes and low-resolution genotyping methods. We aimed to identify HLA alleles linked with longevity by overcoming these previous limitations.
Methods: We performed high-resolution HLA genotyping using targeted sequencing (HLA-seq) in 1,265 long-lived individuals (LLI; ≥94 years) from Germany and compared their HLA allele frequencies to a large control population of 3.4 million individuals from the German Bone Marrow Donor Registry (DKMS) using χ2 (chi-square) tests.
Results: Six HLA alleles were significantly associated with longevity. Of those, two exhibited the most robust associations: A*01:01g (OR=0.87; 95% CI: 0.80-0.95; adj. P=0.02) and DRB1*13:02g (OR=1.24; 95% CI: 1.10-1.41; P=0.01). DRB1*13:02g was replicated in the UK Biobank after Bonferroni correction, whereas A*01:01g showed directionally concordant nominal support but did not remain significant after multiple-testing correction.
Conclusions: Both DRB1*13:02g and A*01:01g have previously been implicated in dementia-related phenotypes. These observations support the hypothesis that HLA variation may influence longevity partly through pathways linked to neurodegeneration. This study provides a high-resolution (2-field) HLA data of a longevity cohort, which would be valuable for future investigations.
Keywords
Longevity, autoimmunity, healthy aging, HLA
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Mejía NM, Kolbe D, Özer O, Dose J, Torres GG, Franke A, et al. Sequence-based HLA genotyping identifies six candidate alleles associated with human longevity in Germans. Geromedicine. 2026;2:202619. https://doi.org/10.70401/Geromedicine.2026.0039
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Mejía NM, Kolbe D, Özer O, Dose J, Torres GG, Franke A, et al. Sequence-based HLA genotyping identifies six candidate alleles associated with human longevity in Germans. Geromedicine. 2026;2:202619. https://doi.org/10.70401/Geromedicine.2026.0039
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