Sidore Carlo, Busonero Fabio, Maschio Andrea, Porcu Eleonora, Naitza Silvia, Zoledziewska Magdalena, Mulas Antonella, Pistis Giorgio, Steri Maristella, Danjou Fabrice, Kwong Alan, Ortega Del Vecchyo Vicente Diego, Chiang Charleston W K, Bragg-Gresham Jennifer, Pitzalis Maristella, Nagaraja Ramaiah, Tarrier Brendan, Brennan Christine, Uzzau Sergio, Fuchsberger Christian, Atzeni Rossano, Reinier Frederic, Berutti Riccardo, Huang Jie, Timpson Nicholas J, Toniolo Daniela, Gasparini Paolo, Malerba Giovanni, Dedoussis George, Zeggini Eleftheria, Soranzo Nicole, Jones Chris, Lyons Robert, Angius Andrea, Kang Hyun M, Novembre John, Sanna Serena, Schlessinger David, Cucca Francesco, Abecasis Gonçalo R
Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
Nat Genet. 2015 Nov;47(11):1272-1281. doi: 10.1038/ng.3368. Epub 2015 Sep 14.
We report ∼17.6 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, ∼76,000 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.
我们报告了对2120名撒丁岛人进行全基因组测序得到的约1760万个基因变异；其中22%未出现在以往基于测序的汇编中，且在预测功能后果方面更为丰富。此外，我们样本中常见的约76000个变异（频率>5%）在其他地方很少见（在千人基因组计划中<0.5%）。我们评估了这些变异对循环脂质水平和五种炎症生物标志物的影响。我们观察到14个与脂质水平相关的信号，包括2个主要的新位点，以及19个与炎症标志物相关的信号，包括2个新位点。基于千人基因组计划数据的分析会遗漏这些新的关联，凸显了在这个奠基者群体中进行大规模测序的优势。
