Suchergebnisse

Supplementary information is available at http://www.nature.com/ncomms/2014/141106/ncomms6345/extref/ncomms6345-s1.pdf ; 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. ; This work was funded by the Wellcome Trust (098051) and the European Research Council (ERC-2011-StG 280559-SEPI). The TEENAGE study has been supported by the Wellcome Trust (098051), European Union (European Social Fund—ESF) and Greek national funds through the Operational Programme 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF)—Research Funding Programme: Heracleitus II, investing in knowledge society through the European Social Fund. G.R.S.R. is supported by the European Molecular Biology Laboratory and the Sanger Institute via an EBI-Sanger Postdoctoral Fellowship. S.F. was supported by H3ABioNet Node, NABDA Abuja Nigeria with NIH Common Fund Award/NHGRI Grant Number U41HG006941 and Genetic Epidemiology Group at WTSI. ; Peer-reviewed ; Publisher Version