TY - JOUR
T1 - A multi-omics study of circulating phospholipid markers of blood pressure
AU - Liu, Jun
AU - de Vries, Paul S
AU - Del Greco M, Fabiola
AU - Johansson, Åsa
AU - Schraut, Katharina E
AU - Hayward, Caroline
AU - van Dijk, Ko Willems
AU - Franco, Oscar H
AU - Hicks, Andrew A
AU - Vitart, Veronique
AU - Rudan, Igor
AU - Campbell, Harry
AU - Polašek, Ozren
AU - Pramstaller, Peter P
AU - Wilson, James F
AU - Gyllensten, Ulf
AU - van Duijn, Cornelia M
AU - Dehghan, Abbas
AU - Demirkan, Ayşe
N1 - Funding Information:
EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006–01947). High-throughput genome-wide association analysis of the data was supported by joint grant from Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Lipidomic analysis was supported by the European Commission FP7 grant LipidomicNet (2007-202272). The CROATIA-VIS study in the Croatian island of Vis was supported through the grants from the Medical Research Council UK (Human Genetics Unit core programme “QTL in health and Disease”, currently MC_UU_00007/10), the Ministry of Science, Education, and Sport of the Republic of Croatia (216–1080315-0302), the Croatian National Center of Research Excellence in Personalized Healthcare (grant number KK.01.1.1.01.0010) and the Center of Competence in Molecular Diagnostics (KK.01.2.2.03.0006). The ERF study was supported by grants from the Netherlands Organisation for Scientific Research (Pionier, 047.016.009, 047.017.043), Erasmus MC, and the Centre for Medical Systems Biology (CMSB; National Genomics Initiative). Ayşe Demirkan was supported by NWO (VENI-91616165), WCRF-2017/1641 and H2020-SC1-2019-874739. The MICROS study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006–018947). The NSPHS study was funded by the Swedish Medical Research Council (Project Number K2007-66X-20270-01-3) and the Foundation for Strategic Research (SSF). NSPHS as part of EUROSPAN (European Special Populations Research Network) was also supported by European Commission FP6 STRP grant number 01947 (LSHG-CT-2006-01947). This work has also been supported by the Swedish Medical Research Council (Project Number 2011-2354), the Göran Gustafssons Foundation, the Swedish Society for Medical Research (SSMF), the Kjell och Märta Beijers Foundation, The Marcus Borgström Foundation, the Åke Wiberg foundation and the Vleugels Foundation. The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government (CZB/4/276, CZB/4/710), a Royal Society URF to J.F.W., the MRC Human Genetics Unit quinquennial programme “QTL in Health and Disease”, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006–018947).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/1/12
Y1 - 2022/1/12
N2 - High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.
AB - High-throughput techniques allow us to measure a wide-range of phospholipids which can provide insight into the mechanisms of hypertension. We aimed to conduct an in-depth multi-omics study of various phospholipids with systolic blood pressure (SBP) and diastolic blood pressure (DBP). The associations of blood pressure and 151 plasma phospholipids measured by electrospray ionization tandem mass spectrometry were performed by linear regression in five European cohorts (n = 2786 in discovery and n = 1185 in replication). We further explored the blood pressure-related phospholipids in Erasmus Rucphen Family (ERF) study by associating them with multiple cardiometabolic traits (linear regression) and predicting incident hypertension (Cox regression). Mendelian Randomization (MR) and phenome-wide association study (Phewas) were also explored to further investigate these association results. We identified six phosphatidylethanolamines (PE 38:3, PE 38:4, PE 38:6, PE 40:4, PE 40:5 and PE 40:6) and two phosphatidylcholines (PC 32:1 and PC 40:5) which together predicted incident hypertension with an area under the ROC curve (AUC) of 0.61. The identified eight phospholipids are strongly associated with triglycerides, obesity related traits (e.g. waist, waist-hip ratio, total fat percentage, body mass index, lipid-lowering medication, and leptin), diabetes related traits (e.g. glucose, insulin resistance and insulin) and prevalent type 2 diabetes. The genetic determinants of these phospholipids also associated with many lipoproteins, heart rate, pulse rate and blood cell counts. No significant association was identified by bi-directional MR approach. We identified eight blood pressure-related circulating phospholipids that have a predictive value for incident hypertension. Our cross-omics analyses show that phospholipid metabolites in the circulation may yield insight into blood pressure regulation and raise a number of testable hypothesis for future research.
U2 - 10.1038/s41598-021-04446-7
DO - 10.1038/s41598-021-04446-7
M3 - Article
C2 - 35022422
SN - 2045-2322
VL - 12
SP - 574
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 574
ER -