The Population-Specific Impact of Neandertal Introgression on Human Disease
Open accessAbstract
Since the discovery of admixture between modern humans and Neandertals, multiple studies investigated the effect of Neandertal-derived DNA on human disease and nondisease phenotypes. These studies have linked Neandertal ancestry to skin- and hair-related phenotypes, immunity, neurological, and behavioral traits. However, these inferences have so far been limited to cohorts with participants of European ancestry. Here, I analyze summary statistics from 40 disease GWAS (genome-wide association study) cohorts of ∼212,000 individuals provided by the Biobank Japan Project for phenotypic effects of Neandertal DNA. I show that Neandertal DNA is associated with autoimmune diseases, prostate cancer and type 2 diabetes. Many of these disease associations are linked to population-specific Neandertal DNA, highlighting the importance of studying a wider range of ancestries to characterize the phenotypic legacy of Neandertals in people today.
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This previous investigation tested whether loci identified from multiple sources were Neanderthal introgressed using the ILS method.
“Considering loci identified from multiple sources, this previous investigation tested whether they were Neanderthal introgressed using the ILS method.”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
The Materials and Methods section describes an ILS-based test for identifying putatively introgressed Neandertal haplotypes. However, it says this study used previously generated haplotype information from the 1,000 Genomes Project; it does not say that the author applied the ILS test to loci identified from multiple sources in this investigation. Page numbers were not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn this previous analysis, Neanderthal-introgressed alleles were defined as those present in modern non-African populations that are shared with the Vindija Neandertal genome using a linkage disequilibrium-based test for incomplete lineage sorting (ILS).
“In this previous analysis, Neanderthal-introgressed alleles were defined as those present in modern non-African populations that are shared with the Vindija Neandertal genome using a linkage disequilibrium-based test for incomplete lineage sorting (ILS).”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
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Experimental — accuracy not yet measuredSignatures of archaic introgression have been reported in genes associated with hair and skin pigmentation, immunity, neoplasms and metabolic traits, and male sterility.
“Additionally, signatures of archaic introgression have been reported in genes associated with hair and skin pigmentation, immunity [16, 17, 19, 20, 22], neoplasms and metabolic traits [19, 23, 24], and male sterility [17, 18].”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
This previous study used a different method to assign Neanderthal-introgressed alleles than the one applied in our study.
“This study used a different method to assign Neanderthal-introgressed alleles than the one applied in our study.”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
Neanderthal-introgressed haplotypes were previously associated with prostate cancer.
“Although this is a novel finding, Neanderthal-introgressed haplotypes were previously associated with prostate cancer [24].”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
Another study investigating Neanderthal-introgressed SNPs in EAS and EUR found multiple associations with autoimmune diseases, prostate cancer, and type 2 diabetes.
“Similarly. another study investigating Neanderthal-introgressed SNPs in EAS and EUR found multiple associations with autoimmune diseases, prostate cancer, and type 2 diabetes [24].”
From Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations (2022) · cites this paper as [24]
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Koller, D., Wendt, F. R., Pathak, G. A., De Lillo, A., De Angelis, F., Cabrera-Mendoza, B., Tucci, S., & Polimanti, R. (2022) · BMC Biology · doi:10.1186/s12915-022-01449-2 · Cited by 27 · see citing works
“another study investigating Neanderthal-introgressed SNPs in EAS and EUR found multiple associations with autoimmune diseases, prostate cancer, and type 2 diabetes [24].”
BackgroundDannemann, M., Milaneschi, Y., Yermakovich, D., Stiglbauer, V., Kariis, H. M., Krebs, K., Friese, M. A., Otte, C., Estonian Biobank Research Team, Esko, T., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02196-2 · Cited by 23 · see citing works
“Testing for the proportional association strength to phenotypes In order to quantify the association strength of archaic variants, we compared their number of significantly associated tag aSNPs to the number of frequency-matched non-archaic tag SNPs following similar approaches that have previously been used for such…”
BackgroundMethodResultInfluentialSelf-citation
- Authors
- Dannemann, M.
- Affiliations
- University of Tartu (EE)
- Corresponding author
- Dannemann, Michael
- ORCID
- Dannemann, Michael
- Venue
- Genome Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-01
- Volume
- 13
- Issue
- 1
- ISSN
- 1759-6653 (ISSN-L)
- PMC
- PMC7851588
- OpenAlex
- W3107733243
- Cited by
- 33
- References
- 12
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 9 · 2022: 7 · 2021: 3
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome Biology and Evolution (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- European Union (810645)
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- human disease, autoimmune disease, prostate cancer, type 2 diabetes
- MeSH terms
- Alleles, Animals, Diabetes Mellitus, Type 2, Disease, Female, Fossils, Humans, Japan, Male, Phenotype, Genetic Variation, Genome, Human, Evolution, Molecular, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Neanderthals
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