Title |
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans
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Published in |
Nature Communications, September 2014
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DOI | 10.1038/ncomms5871 |
Pubmed ID | |
Authors |
Nicholas J. Timpson, Klaudia Walter, Josine L. Min, Ioanna Tachmazidou, Giovanni Malerba, So-Youn Shin, Lu Chen, Marta Futema, Lorraine Southam, Valentina Iotchkova, Massimiliano Cocca, Jie Huang, Yasin Memari, Shane McCarthy, Petr Danecek, Dawn Muddyman, Massimo Mangino, Cristina Menni, John R. B. Perry, Susan M. Ring, Amadou Gaye, George Dedoussis, Aliki-Eleni Farmaki, Paul Burton, Philippa J. Talmud, Giovanni Gambaro, Tim D. Spector, George Davey Smith, Richard Durbin, J Brent Richards, Steve E. Humphries, Eleftheria Zeggini, Nicole Soranzo |
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 APOC3 (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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 27% |
United Kingdom | 2 | 9% |
Netherlands | 1 | 5% |
Spain | 1 | 5% |
Canada | 1 | 5% |
Japan | 1 | 5% |
Nigeria | 1 | 5% |
India | 1 | 5% |
Unknown | 8 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 55% |
Scientists | 10 | 45% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 1% |
United States | 2 | 1% |
Japan | 1 | <1% |
Finland | 1 | <1% |
Unknown | 138 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 36 | 25% |
Student > Ph. D. Student | 18 | 13% |
Professor > Associate Professor | 13 | 9% |
Other | 11 | 8% |
Student > Bachelor | 10 | 7% |
Other | 29 | 20% |
Unknown | 27 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 38 | 26% |
Biochemistry, Genetics and Molecular Biology | 30 | 21% |
Medicine and Dentistry | 29 | 20% |
Computer Science | 4 | 3% |
Psychology | 2 | 1% |
Other | 8 | 6% |
Unknown | 33 | 23% |