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

Kalliope Panoutsopoulou, Konstantinos Hatzikotoulas, Dionysia Kiara Xifara, Vincenza Colonna, Aliki Eleni Farmaki, Graham R.S. Ritchie, Lorraine Southam, Arthur Gilly, Ioanna Tachmazidou, Segun Fatumo, Angela Matchan, Nigel W. Rayner, Ioanna Ntalla, Massimo Mezzavilla, Yuan Chen, Chrysoula Kiagiadaki, Eleni Zengini, Vasiliki Mamakou, Antonis Athanasiadis, Margarita GiannakopoulouVassiliki Eirini Kariakli, Rebecca N. Nsubuga, Alex Karabarinde, Manjinder Sandhu, Gil McVean, Chris Tyler-Smith, Emmanouil Tsafantakis, Maria Karaleftheri, Yali Xue, George Dedoussis, Eleftheria Zeggini

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45 Scopus citations

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.

Original languageEnglish
Article number5345
JournalNature Communications
Volume5
DOIs
StatePublished - 2014
Externally publishedYes

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