SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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

Timpson, NJ; Walter, K; Min, JL; Tachmazidou, I; Malerba, G; Shin, S-Y; Chen, L; Futema, M; Southam, L; Iotchkova, V; et al. Timpson, NJ; Walter, K; Min, JL; 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, JRB; Ring, SM; Gaye, A; Dedoussis, G; Farmaki, A-E; Burton, P; Talmud, PJ; Gambaro, G; Spector, TD; Smith, GD; Durbin, R; Richards, JB; Humphries, SE; Zeggini, E; Soranzo, N; UK1OK Consortium Members; UK1OK Consortium Members (2014) A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nat Commun, 5. p. 4871. ISSN 2041-1723 https://doi.org/10.1038/ncomms5871
SGUL Authors: Jamshidi, Yalda

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (554kB) | Preview

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.

Item Type: Article
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Erratum available at https://doi.org/10.1038/ncomms8171
Keywords: Alleles, Alternative Splicing, Apolipoprotein C-III, Child, European Continental Ancestry Group, Female, Gene Frequency, Humans, Lipoproteins, HDL, Lipoproteins, VLDL, Male, Middle Aged, Polymorphism, Genetic, Triglycerides, Twins, UK1OK Consortium Members, UK1OK Consortium Members, Humans, Triglycerides, Lipoproteins, HDL, Lipoproteins, VLDL, Alternative Splicing, Twins, Gene Frequency, Polymorphism, Genetic, Alleles, Middle Aged, Child, European Continental Ancestry Group, Female, Male, Apolipoprotein C-III, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Nat Commun
ISSN: 2041-1723
Language: eng
Dates:
DateEvent
16 September 2014Published
30 July 2014Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
G1001799Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12013/1-9Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
092731Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0601635Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
102215Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_UU_12013/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
090532Wellcome Trusthttp://dx.doi.org/10.13039/100004440
280559European Research Councilhttp://dx.doi.org/10.13039/501100000781
095515Wellcome Trusthttp://dx.doi.org/10.13039/100004440
100574Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PG008/08British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RG/10/13/28570British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
MR/L010305/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G9815508Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
WT095219MAWellcome Trusthttp://dx.doi.org/10.13039/100004440
RG/08/008/25291British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
MC_UU_12013/3Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
095219Wellcome Trusthttp://dx.doi.org/10.13039/100004440
096599Wellcome Trusthttp://dx.doi.org/10.13039/100004440
076113Wellcome Trusthttp://dx.doi.org/10.13039/100004440
098051Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_PC_15018Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
091310Wellcome Trusthttp://dx.doi.org/10.13039/100004440
RG/10/17/28553British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
G0800509Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
091551Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 25225788
Web of Science ID: WOS:000342930300011
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112986
Publisher's version: https://doi.org/10.1038/ncomms5871

Actions (login required)

Edit Item Edit Item