RT Journal Article
SR Electronic
T1 Genome-wide association study of plasma triglycerides, phospholipids and relation to cardio-metabolic risk factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 621334
DO 10.1101/621334
A1 Ayşe Demirkan
A1 Rene Pool
A1 Joris Deelen
A1 Marian Beekman
A1 Jun Liu
A1 Amy C. Harms
A1 Anika Vaarhorst
A1 Fiona A Hagenbeek
A1 Gonneke Willemsen
A1 Aswin Verhoeven
A1 Najaf Amin
A1 Ko Willems van Dijk
A1 Thomas Hankemeier
A1 Dorret I. Boomsma
A1 Eline Slagboom
A1 Cornelia M. van Duijn
YR 2019
UL http://biorxiv.org/content/early/2019/06/22/621334.abstract
AB There is continuous interest in the genetic determinants of plasma triglycerides (TGs) and phospholipids and their role in the etiology of cardiovascular disease (CVD). Here, we report the results of a Dutch genome wide association study (GWAS) of an in-house developed lipidomics platform, focusing on 90 plasma lipids. Lipids were assessed by liquid chromatography mass spectrometry in participants from the Leiden Longevity Study, the Netherlands Twin Register and the Erasmus Rucphen Family (ERF) study and meta-analysed, resulting in a sample size of 5537 participants. In addition, we performed genetic correlation analyses between the 90 plasma lipids and markers of metabolic health, as well as vascular pathology and CVD combining our GWAS results with publicly available GWAS outputs. We replicated previously known associations between 34 lipids and 10 lipid quantitative trait loci (lipQTL) (GCKR, APOA1, FADS1, SGPP1,TMEM229B, LIPC, PDXDC1, CETP, CERS4 and SPTLC3) with metabolome-wide (P < 1.61 × 10−9) significance. Moreover, we report 6 novel phospholipid-related and 5 triglyceride (TG)-related loci: SGGP1 (SM21:0), SPTLC3 (SM21:0 and SM25:1), FADS1 (LPCO16:1, PC38:2, PEO36:5, PEO38:5, TG56:5, TG56:6, and TG56:7), TMEM229 (LPCO16:1), GCKR (TG50:2), and APOA1 (TG54:4). In addition, we report suggestively significant (P < 5 × 10−8) associations mapping to eleven novel lipid quantitative trait loci (lipQTLs), three of which are supported by mining previous GWAS data: MAU (PC34:4), LDLR (SM16:0), and MLXIPL (TG48:1 and TG50:1)). Genetic correlation analysis indicates that one specific specific sphingomyelin, SM22:0, shares common genetic background with CVD. Levels of SM22:0 also positively associate with carotid artery intima-media thickness in the ERF study, and this observation is independent of LDL-C level. Our findings yield higher resolution of plasma lipid species and new insights in the biology of circulating phosholipids and their relation to CVD risk.