TY - JOUR T1 - Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations. JF - Nat Commun Y1 - 2017 A1 - Xue, Yali A1 - Mezzavilla, Massimo A1 - Haber, Marc A1 - McCarthy, Shane A1 - Chen, Yuan A1 - Narasimhan, Vagheesh A1 - Gilly, Arthur A1 - Ayub, Qasim A1 - Colonna, Vincenza A1 - Southam, Lorraine A1 - Finan, Christopher A1 - Massaia, Andrea A1 - Chheda, Himanshu A1 - Palta, Priit A1 - Ritchie, Graham A1 - Asimit, Jennifer A1 - Dedoussis, George A1 - Gasparini, Paolo A1 - Palotie, Aarno A1 - Ripatti, Samuli A1 - Soranzo, Nicole A1 - Toniolo, Daniela A1 - Wilson, James F A1 - Durbin, Richard A1 - Tyler-Smith, Chris A1 - Zeggini, Eleftheria KW - European Continental Ancestry Group KW - Gene Frequency KW - Genetic Variation KW - Genetics, Population KW - Genome, Human KW - Humans KW - Polymorphism, Single Nucleotide KW - Whole Genome Sequencing AB -

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.

VL - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28643794?dopt=Abstract ER -