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Nat Genet. 2015 Nov;47(11):1272-81. doi: 10.1038/ng.3368. Epub 2015 Sep 14.

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

Author information

1
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
2
Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
3
Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy.
4
DNA Sequencing Core, University of Michigan, Ann Arbor, Michigan, USA.
5
Interdepartmental Program in Bioinformatics, University of California, Los Angeles, Los Angeles, California, USA.
6
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California, USA.
7
Laboratory of Genetics, National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.
8
Porto Conte Ricerche, Tramariglio, Alghero, Italy.
9
Center for Advanced Studies, Research and Development in Sardinia (CRS4), Parco Scientifico e Tecnologico della Sardegna, Pula, Italy.
10
Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
11
Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
12
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
13
Dipartimento di Salute Mentale, University of Trieste and IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Burlo Garofolo Children Hospital, Trieste, Italy.
14
Experimental Genetics Division, Sidra, Doha, Qatar.
15
Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
16
Department of Nutrition and Dietetics, Harokopio University Athens, Athens, Greece.
17
Department of Haematology, University of Cambridge, Cambridge, UK.
18
Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.

Abstract

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.

PMID:
26366554
PMCID:
PMC4627508
DOI:
10.1038/ng.3368
[Indexed for MEDLINE]
Free PMC Article

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