A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates

被引：68

作者：

Tachmazidou, Ioanna ^{[1
]}

Dedoussis, George ^{[2
]}

Southam, Lorraine ^{[1
,3
]}

Farmaki, Aliki-Eleni ^{[2
]}

Ritchie, Graham R. S. ^{[1
,4
]}

Xifara, Dionysia K. ^{[3
,5
]}

Matchan, Angela ^{[1
]}

Hatzikotoulas, Konstantinos ^{[1
]}

Rayner, Nigel W. ^{[1
,3
]}

Chen, Yuan ^{[1
]}

Pollin, Toni I. ^{[6
]}

O'Connell, Jeffrey R. ^{[6
]}

Yerges-Armstrong, Laura M. ^{[6
]}

Kiagiadaki, Chrysoula ^{[7
]}

Panoutsopoulou, Kalliope ^{[1
]}

Schwartzentruber, Jeremy ^{[1
]}

Moutsianas, Loukas ^{[3
]}

Tsafantakis, Emmanouil ^{[7
]}

Tyler-Smith, Chris ^{[1
]}

McVean, Gil ^{[3
]}

Xue, Yali ^{[1
]}

Zeggini, Eleftheria ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[2] Univ Athens, Dept Dietet Nutr, Athens 17671, Greece

[3] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[4] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, England

[5] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[6] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[7] Anogia Med Ctr, Anogia 74051, Greece

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

欧洲研究理事会; 英国惠康基金;

关键词：

APOLIPOPROTEIN-C-III; CORONARY-HEART-DISEASE; GENETIC-VARIATION; LOCI; PROMOTER; INSULIN; PLASMA; COMMON; HYPERTRIGLYCERIDEMIA; IDENTIFICATION;

D O I：

10.1038/ncomms3872

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search of functional coding variants associated with lipids traits. We find genome-wide significant evidence for association between R19X, a functional variant in APOC3, with increased high-density lipoprotein and decreased triglycerides levels. Approximately 3.8% of individuals are heterozygous for this cardioprotective variant, which was previously thought to be private to the Amish founder population. R19X is rare (<0.05% frequency) in outbred European populations. The increased frequency of R19X enables discovery of this lipid traits signal at genome-wide significance in a small sample size. This work exemplifies the value of isolated populations in successfully detecting transferable rare variant associations of high medical relevance.

引用

页数：6

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