Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Harshfield, Eric L
Fauman, Eric B
Stacey, David
Ziemek, Daniel
Abstract
Background
Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies.Methods
We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci.Results
We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci.Conclusions
Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.Description
Funder: Pfizer
Funder: Novartis
Funder: National Institute for Health Research
Funder: Merck
Keywords
Genetics, Lipidomics, Network Analysis, South Asian, Gaussian Graphical Modelling
Journal Title
BMC medicine
Conference Name
Journal ISSN
1741-7015
Volume Title
19
Publisher
Publisher DOI
Sponsorship
Wellcome Trust (105602/Z/14/Z)
British Heart Foundation (SP/09/002, RG/18/13/33946, RG/13/13/30194)
Medical Research Council (MC_PC_13030, MC_UP_A090_1006, G0800270, G0800783, MR/L003120/1)
Sixth Framework Programme (Bloodomics Integrated Project)
British Heart Foundation (SP/09/002, RG/18/13/33946, RG/13/13/30194)
Medical Research Council (MC_PC_13030, MC_UP_A090_1006, G0800270, G0800783, MR/L003120/1)
Sixth Framework Programme (Bloodomics Integrated Project)