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

被引：268

作者：

Sidore, Carlo ^{[1
,2
,3
]}

Busonero, Fabio ^{[1
,2
,4
]}

Maschio, Andrea ^{[1
,2
,4
]}

Porcu, Eleonora ^{[1
,2
,3
]}

Naitza, Silvia ^{[1
]}

Zoledziewska, Magdalena ^{[1
]}

Mulas, Antonella ^{[1
,3
]}

Pistis, Giorgio ^{[1
,2
,3
]}

Steri, Maristella ^{[1
]}

Danjou, Fabrice ^{[1
]}

Kwong, Alan ^{[2
]}

del Vecchyo, Vicente Diego Ortega ^{[5
]}

Chiang, Charleston W. K. ^{[6
]}

Bragg-Gresham, Jennifer ^{[2
]}

Pitzalis, Maristella ^{[1
]}

Nagaraja, Ramaiah ^{[7
]}

Tarrier, Brendan ^{[4
]}

Brennan, Christine ^{[4
]}

Uzzau, Sergio ^{[8
]}

Fuchsberger, Christian ^{[2
]}

Atzeni, Rossano ^{[9
]}

Reinier, Frederic ^{[9
]}

Berutti, Riccardo ^{[3
,9
]}

Huang, Jie ^{[10
]}

Timpson, Nicholas J. ^{[11
]}

Toniolo, Daniela ^{[12
]}

Gasparini, Paolo ^{[13
,14
,15
]}

Malerba, Giovanni ^{[16
]}

Dedoussis, George ^{[17
]}

Zeggini, Eleftheria ^{[10
]}

Soranzo, Nicole ^{[10
,18
]}

Jones, Chris ^{[9
]}

Lyons, Robert ^{[4
]}

Angius, Andrea ^{[1
,9
]}

Kang, Hyun M. ^{[2
]}

Novembre, John ^{[19
]}

Sanna, Serena ^{[1
]}

Schlessinger, David ^{[7
]}

Cucca, Francesco ^{[1
,3
]}

Abecasis, Goncalo R. ^{[2
]}

机构：

[1] CNR, Ist Ric Genet & Biomed, Cagliari, Italy

[2] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[3] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy

[4] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA

[5] Univ Calif Los Angeles, Interdept Program Bioinformat, Los Angeles, CA USA

[6] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA

[7] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA

[8] Porto Conte Ric, Tramariglio, Alghero, Italy

[9] Parco Sci & Tecnol Sardegna, Res & Dev Sardinia CRS4, Ctr Adv Studies, Pula, Italy

[10] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England

[11] Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England

[12] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy

[13] Univ Trieste, Dipartimento Salute Mentale, Trieste, Italy

[14] Burlo Garofolo Children Hosp, Ist Ricovero & Cura Carattere Sci, Trieste, Italy

[15] Sidra, Expt Genet Div, Doha, Qatar

[16] Univ Verona, Dept Life & Reprod Sci, I-37100 Verona, Italy

[17] Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece

[18] Univ Cambridge, Dept Haematol, Cambridge, England

[19] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

基金：

美国国家卫生研究院; 英国惠康基金; 欧洲研究理事会;

关键词：

C-REACTIVE PROTEIN; WIDE ASSOCIATION; GENOTYPE IMPUTATION; COMPLEX TRAITS; HEART-DISEASE; VARIANTS; POPULATION; MULTIPLE; RISK; HERITABILITY;

D O I：

10.1038/ng.3368

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report similar to 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, similar to 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.

引用

页码：1272 / +

页数：13

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