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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms8171

Nature Research, Nature Communications, 1(5), 2014

DOI: 10.1038/ncomms5871

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

Journal article published in 2014 by Nicholas J. Timpson ORCID, Josine L. Min, Klaudia K. H. Walter, So-Youn Shin, Eleftheria Zeggini ORCID, Timpson Nj, Saeed Al Turki, Maria Soler Artigas, Ioanna Tachmazidou, Carl A. Anderson, J. B. Richards, Richard J. L. Anney, Dinu Antony, Giovanni Malerba, Muhammad K. Ayub and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractThe 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.