Evidence of Polygenic Adaptation in Sardinia at Height-Associated Loci Ascertained from the Biobank Japan
Open accessAbstract
Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10-4). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10-4). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.
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Within-sibship GWAS data are robust against population stratification.
“Within-sibship GWAS data are particularly useful in this context as they are robust against population stratification26,27,29.”
From Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects (2022) · cites this paper as [29]
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- Authors
- Chen, M., Sidore, C., Akiyama, M., Ishigaki, K., Kamatani, Y., Schlessinger, D., Cucca, F., Okada, Y., & Chiang, C. W. K.
- Affiliations
- University of Southern California (US)
- Institute of Genetic and Biomedical Research (IT)
- Kyushu University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Kyoto University (JP)
- National Institutes of Health (US)
- Corresponding author
- Chen, Minhui
- Chiang, Charleston W.K.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 107
- Issue
- 1
- Pages
- 60-71
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC7332648
- OpenAlex
- W3035648213
- Cited by
- 32
- References
- 44
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- polygenic adaptation, adult height, Sardinians, polygenic risk score, population divergence, East Asian populations, Biobank Japan, genetic stratification, European populations
- MeSH terms
- Adaptation, Physiological, Alleles, Body Height, Genetics, Population, Haplotypes, Humans, Italy, Japan, Phenotype, Selection, Genetic, Genome, Human, Biological Specimen Banks, Multifactorial Inheritance, Polymorphism, Single Nucleotide, White People, Asian People, Genome-Wide Association Study
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