A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

Timpson, Nicholas J., Walter, Klaudia, Min, Josine L., Tachmazidou, Ioanna, Malerba, Giovanni, Shin, So-Youn, Chen, Lu, Futema, Marta, Southam, Lorraine, Iotchkova, Valentina, Cocca, Massimiliano, Huang, Jie, Memari, Yasin, McCarthy, Shane, Danecek, Petr, Muddyman, Dawn, Mangino, Massimo, Menni, Cristina, Perry, John R. B., Ring, Susan M., Gaye, Amadou, Dedoussis, George, Farmaki, Aliki-Eleni, Burton, Paul, Talmud, Philippa J., Gambaro, Giovanni, Spector, Tim D., Smith, George Davey, Durbin, Richard, Richards, J. Brent, Humphries, Steve E., Zeggini, Eleftheria, Soranzo, Nicole, UK10K Consortium, Evans, David, Kemp, John, Visscher, Peter M. and Yang, Jian (2014) A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nature Communications, 5 1-10. doi:10.1038/ncomms5871

Author Timpson, Nicholas J.
Walter, Klaudia
Min, Josine L.
Tachmazidou, Ioanna
Malerba, Giovanni
Shin, So-Youn
Chen, Lu
Futema, Marta
Southam, Lorraine
Iotchkova, Valentina
Cocca, Massimiliano
Huang, Jie
Memari, Yasin
McCarthy, Shane
Danecek, Petr
Muddyman, Dawn
Mangino, Massimo
Menni, Cristina
Perry, John R. B.
Ring, Susan M.
Gaye, Amadou
Dedoussis, George
Farmaki, Aliki-Eleni
Burton, Paul
Talmud, Philippa J.
Gambaro, Giovanni
Spector, Tim D.
Smith, George Davey
Durbin, Richard
Richards, J. Brent
Humphries, Steve E.
Zeggini, Eleftheria
Soranzo, Nicole
UK10K Consortium
Evans, David
Kemp, John
Visscher, Peter M.
Yang, Jian
Total Author Count Override 6698
Title A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans
Formatted title
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2014-09-16
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ncomms5871
Open Access Status DOI
Volume 5
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Formatted abstract
The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in ‚ÄčAPOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (−1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10−8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (−1.0 s.d. (s.e.=0.173), P-value=7.32 × 10−9). This is consistent with an effect between 0.5 and 1.5 mmol l−1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # 4871

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
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Created: Wed, 25 Mar 2015, 14:02:01 EST by Kylie Hengst on behalf of Queensland Brain Institute