A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.
AuthorTimpson, NJ; Walter, K; Min, JL; Tachmazidou, I; Malerba, G; Shin, S-Y; Chen, L; Futema, M; Southam, L; Iotchkova, V; ...
Source TitleNature Communications
PublisherSpringer Science and Business Media LLC
University of Melbourne Author/sKaye, Jane
AffiliationMelbourne Law School
Document TypeJournal Article
CitationsTimpson, N. J., Walter, K., Min, J. L., Tachmazidou, I., Malerba, G., Shin, S. -Y., Chen, L., Futema, M., Southam, L., Iotchkova, V., Cocca, M., Huang, J., Memari, Y., McCarthy, S., Danecek, P., Muddyman, D., Mangino, M., Menni, C., Perry, J. R. B. ,... UK1OK Consortium Members (2014). A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.. Nat Commun, 5 (1), pp.4871-. https://doi.org/10.1038/ncomms5871.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167609
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.
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