title: Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers.
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.
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.|Università degli Studi di Sassari, Sassari, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sidore
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.|University of Michigan, DNA Sequencing Core, Ann Arbor, MI, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Busonero
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.|University of Michigan, DNA Sequencing Core, Ann Arbor, MI, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maschio
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.|Università degli Studi di Sassari, Sassari, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Porcu
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Naitza
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zoledziewska
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Università degli Studi di Sassari, Sassari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mulas
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.|Università degli Studi di Sassari, Sassari, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pistis
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Steri
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Danjou
authors.affiliation: Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Kwong
authors.affiliation: Interdepartmental Program in Bioinformatics, University of California - Los Angeles, CA,USA.
authors.forename: Vicente Diego
authors.initials: VD
authors.lastname: Ortega Del Vecchyo
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA.
authors.forename: Charleston W K
authors.initials: CWK
authors.lastname: Chiang
authors.affiliation: Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bragg-Gresham
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Pitzalis
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Ramaiah
authors.initials: R
authors.lastname: Nagaraja
authors.affiliation: University of Michigan, DNA Sequencing Core, Ann Arbor, MI, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Tarrier
authors.affiliation: University of Michigan, DNA Sequencing Core, Ann Arbor, MI, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Brennan
authors.affiliation: Porto Conte Ricerche srl, Tramariglio, Alghero, 07041 Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Uzzau
authors.affiliation: Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Fuchsberger
authors.affiliation: Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy.
authors.forename: Rossano
authors.initials: R
authors.lastname: Atzeni
authors.affiliation: Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy.
authors.forename: Frederic
authors.initials: F
authors.lastname: Reinier
authors.affiliation: Università degli Studi di Sassari, Sassari, Italy.|Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Berutti
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1HH.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.affiliation: DSM-University of Trieste and IRCCS-Burlo Garofolo Children Hospital (Trieste, Italy).|Experimental Genetics Division, Sidra, (Doha, Qatar).
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.affiliation: Harokopio University Athens.
authors.forename: George
authors.initials: G
authors.lastname: Dedoussis
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1HH.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1HH.|Department of Haematology, University of Cambridge, Hills Rd, Cambridge CB2 0AH.
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy.
authors.forename: Chris
authors.initials: C
authors.lastname: Jones
authors.affiliation: University of Michigan, DNA Sequencing Core, Ann Arbor, MI, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lyons
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Center for Advanced Studies, Research, and Development in Sardinia (CRS4), AGCT Program, Parco Scientifico e tecnologico della Sardegna, Pula, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Angius
authors.affiliation: Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
authors.forename: Hyun M
authors.initials: HM
authors.lastname: Kang
authors.affiliation: Department of Human Genetics, University of Chicago, IL, USA.
authors.forename: John
authors.initials: J
authors.lastname: Novembre
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Cagliari, Italy.|Università degli Studi di Sassari, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
authors.affiliation: Center for Statistical Genetics, Ann Arbor, University of Michigan, MI, USA.
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005843:Geography; D006239:Haplotypes; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007558:Italy; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D008055:Lipids