Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

Carlo Sidore, Fabio Busonero, Andrea Maschio, Eleonora Porcu, Silvia Naitza, Magdalena Zoledziewska, Antonella Mulas, Giorgio Pistis, Maristella Steri, Fabrice Danjou, Alan Kwong, Vicente Diego Ortega Del Vecchyo, Charleston W.K. Chiang, Jennifer Bragg-Gresham, Maristella Pitzalis, Ramaiah Nagaraja, Brendan Tarrier, Christine Brennan, Sergio Uzzau, Christian FuchsbergerRossano Atzeni, Frederic Reinier, Riccardo Berutti, Jie Huang, Nicholas J. Timpson, Daniela Toniolo, Paolo Gasparini, Giovanni Malerba, George Dedoussis, Eleftheria Zeggini, Nicole Soranzo, Chris Jones, Robert Lyons, Andrea Angius, Hyun M. Kang, John Novembre, Serena Sanna, David Schlessinger, Francesco Cucca, Gonçalo R. Abecasis

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

We report -1/417.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, -1/476,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population.

Original languageEnglish
Pages (from-to)1272-1281
Number of pages10
JournalNature Genetics
Volume47
Issue number11
DOIs
StatePublished - 1 Nov 2015
Externally publishedYes

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