Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants.
| Title | Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Panoutsopoulou, K., Hatzikotoulas K., Xifara D. Kiara, 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. |
| Journal | Nat Commun |
| Volume | 5 |
| Pagination | 5345 |
| Date Published | 2014 |
| ISSN | 2041-1723 |
| Keywords | Adolescent, Blood Cells, Cell Size, Cohort Studies, Gene Frequency, Genetic Drift, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Genotype, Greece, Haplotypes, Humans, Mutation, Missense, Phenotype, Population, Social Isolation |
| 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. |
| DOI | 10.1038/ncomms6345 |
| Alternate Journal | Nat Commun |
| PubMed ID | 25373335 |
| PubMed Central ID | PMC4242463 |
| Grant List | 098051 / / Wellcome Trust / United Kingdom 098051 / / Wellcome Trust / United Kingdom 280559 / / European Research Council / International U41 HG006941 / HG / NHGRI NIH HHS / United States U41HG006941 / HG / NHGRI NIH HHS / United States |
