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

作者：Panoutsopoulou Kalliope; Hatzikotoulas Konstantinos; Xifara Dionysia Kiara; Colonna Vincenza; Farmaki Aliki Eleni; Ritchie Graham R S; Southam Lorraine; Gilly Arthur; Tachmazidou Ioanna; Fatumo Segun; Matchan Angela; Rayner Nigel W; Ntalla Ioanna; Mezzavilla Massimo; Chen Yuan; Kiagiadaki Chrysoula; Zengini Eleni; Mamakou Vasiliki; Athanasiadis Antonis; Giannakopoulou Margarita; Kariakli Vassiliki Eirini; Nsubuga Rebecca N; Karabarinde Alex; Sandhu Manjinder

来源：Nature Communications, 2014, 5(1): 5345.

DOI：10.1038/ncomms6345

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 x 10(-26)). We replicate this association in a second set of Pomak samples (combined P = 2.0 x 10(-36)). We demonstrate significant power gains in detecting medical trait associations.

• 出版日期2014-11