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Cited by 70Genetic Associations and EpidemiologyForensic and Genetic ResearchGenetic diversity and population structure

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants

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Panoutsopoulou, Kalliope, Hatzikotoulas, Konstantinos, Xifara, Dionysia Kiara, Colonna, Vincenza, Farmaki, Aliki-Eleni, Ritchie, Graham R. S., Southam, Lorraine, Gilly, Arthur +23 more·2014·Nature Communications
DOI 10.1038/ncomms6345PMC PMC4242463
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Abstract

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10−26). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10−36). We demonstrate significant power gains in detecting medical trait associations.

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  • The lack of replication of Png et al. associations may be due to partial overlap between assayed protein sets, cohort differences (European ancestry vs a Greek population isolate with population-specific CNVs), and differences in CNV detection approach.

    “possibly because there was only a partial overlap between the assayed protein sets, differences between cohorts (European ancestry vs a Greek population isolate with population-specific CNVs)76, and differences in the approach used for CNV detection.”

    From Genetic determinants of plasma protein levels in the Estonian population (2024) · cites this paper as [76]

    The Abstract and Discussion identify the studied Greek cohorts as genetic isolates, supporting the cohort distinction for which this citation is placed. Our copy describes drifted SNPs and missense variants, but does not establish that these cohorts have population-specific CNVs. The citation is attached to the cohort comparison, not the separate explanations about protein-set overlap or CNV detection. (LLM, conf=0.86)

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Authors
Panoutsopoulou, K., Hatzikotoulas, K., Xifara, D. K., Colonna, V., Farmaki, A.-E., Ritchie, G. R. S., Southam, L., Gilly, A., Tachmazidou, I., Fatumo, S., Matchan, A., Rayner, N. W., Ntalla, I., Mezzavilla, M., Chen, Y., Kiagiadaki, C., Zengini, E., Mamakou, V., Athanasiadis, A., Giannakopoulou, M., Kariakli, V.-E., Nsubuga, R. N., Karabarinde, A., Sandhu, M., McVean, G., Tyler-Smith, C., Tsafantakis, E., Karaleftheri, M., Xue, Y., Dedoussis, G., & Zeggini, E.
Affiliations
  • Wellcome Sanger Institute (GB)
  • Centre for Human Genetics (GB)
  • Institute of Genetics and Biophysics (IT)
  • Harokopio University of Athens (GR)
  • European Bioinformatics Institute (GB)
  • University of Cambridge (GB)
  • University of Trieste (IT)
  • Adana Hospital (TR)
  • University of Sheffield (GB)
  • National and Kapodistrian University of Athens (GR)
  • MRC/UVRI & LSHTM Uganda Research Unit (UG)
Corresponding author
Zeggini, Eleftheria
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2014-11-06
Volume
5
Issue
1
Pages
5345-5345
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms6345
PMC
PMC4242463
OpenAlex
W2090216893
Cited by
70
References
5
Citations by year
2026: 4 · 2025: 7 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 2 · 2019: 8 · 2018: 10 · 2017: 5 · 2016: 11 · 2015: 3 · 2014: 1
FWCI
4.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Leicester Research Archive (University of Leicester) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (098051)
  • European Molecular Biology Laboratory
  • European Commission
  • National Human Genome Research Institute (U41HG006941)
  • European Social Fund
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 › Genetic diversity and population structure
Keywords
isolated populations, genetic drift, missense mutations, rare variants, Pomaks, hematological traits, mean corpuscular volume, population genomics
MeSH terms
Adolescent, Blood Cells, Gene Frequency, Genetics, Population, Genotype, Greece, Haplotypes, Humans, Phenotype, Population, Social Isolation, Genetic Variation, Cohort Studies, Mutation, Missense, Genetic Drift, Cell Size, Genome-Wide Association Study

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