In:
Nature Communications, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2014-09-16)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-1723
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2014
ZDB Id:
2553671-0
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