Projects per year
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.
Original language | English |
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Pages (from-to) | 4871 |
Journal | Nature Communications |
Volume | 5 |
DOIs | |
Publication status | Published - 16 Sept 2014 |
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Dive into the research topics of 'A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans'. Together they form a unique fingerprint.Projects
- 3 Finished
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MRC UoB UNITE Unit - programme 3
Timpson, N. J. (Principal Investigator) & Timpson, N. J. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
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MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research
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Profiles
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Professor Nicholas John Timpson
- Bristol Medical School (PHS) - Professor of Genetic Epidemiology
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member