TY - JOUR
T1 - Genetic architecture of human plasma lipidome and its link to cardiovascular disease
AU - FinnGen Project
AU - Tabassum, Rubina
AU - Rämö, Joel T.
AU - Ripatti, Pietari
AU - Koskela, Jukka T.
AU - Kurki, Mitja
AU - Karjalainen, Juha
AU - Palta, Priit
AU - Hassan, Shabbeer
AU - Nunez-Fontarnau, Javier
AU - Kiiskinen, Tuomo T.J.
AU - Söderlund, Sanni
AU - Matikainen, Niina
AU - Gerl, Mathias J.
AU - Surma, Michal A.
AU - Klose, Christian
AU - Stitziel, Nathan O.
AU - Laivuori, Hannele
AU - Havulinna, Aki S.
AU - Service, Susan K.
AU - Salomaa, Veikko
AU - Pirinen, Matti
AU - Jalanko, Anu
AU - Kaprio, Jaakko
AU - Donner, Kati
AU - Kaunisto, Mari
AU - Mars, Nina
AU - Dada, Alexander
AU - Shcherban, Anastasia
AU - Ganna, Andrea
AU - Lehisto, Arto
AU - Kilpeläinen, Elina
AU - Brein, Georg
AU - Awaisa, Ghazal
AU - Harju, Jarmo
AU - Pärn, Kalle
AU - Parolo, Pietro Della Briotta
AU - Kajanne, Risto
AU - Lemmelä, Susanna
AU - Sipilä, Timo P.
AU - Sipilä, Tuomas
AU - Lyhs, Ulrike
AU - Llorens, Vincent
AU - Niiranen, Teemu
AU - Kristiansson, Kati
AU - Männikkö, Lotta
AU - Jiménez, Manuel González
AU - Perola, Markus
AU - Wong, Regis
AU - Kilpi, Terhi
AU - Hiekkalinna, Tero
N1 - Funding Information:
We would like to thank Sari Kivikko, Huei-Yi Shen and Ulla Tuomainen for management assistance. We thank all study participants of the study for their participation. The FINRISK and FinnGen data used for the research were obtained from THL Biobank. We thank the THL DNA laboratory for its skillful work to produce the DNA samples used in the genotyping work, which was used in this study. Part of the genotyping was performed by the Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This research has been conducted using the UK Biobank Resource with application number 22627. This work was supported by National Institutes of Health [grant HL113315 to S.R., M.R.T., N.F. and A.P.]; Finnish Foundation for Cardiovascular Research [to S.R., V.S., M.R.T., M.J. and A.P.]; Academy of Finland Center of Excellence in Complex Disease Genetics [grant 312062 to S.R.]; Academy of Finland [285380 to S.R., 288509 to M.P.]; Jane and Aatos Erkko Foundation [to M.J.]; Sigrid Jusélius Foundation [to S.R. and M.R.T.]; Horizon 2020 Research and Innovation Programme [grant 692145 to S.R.]; EU-project RESOLVE (EU 7th Framework Programme) [grant 305707 to M.R. T.]; HiLIFE Fellowship [to S.R.]; Helsinki University Central Hospital Research Funds [to M.R.T.]; Magnus Ehrnrooth Foundation [to M.J.]; Leducq Foundation [to M.R.T.]; Ida Montin Foundation [to P.R.]; MD-PhD Programme of the Faculty of Medicine, University of Helsinki [to J.T.R.]; Doctoral Programme in Population Health, University of Helsinki [to J.T.R. and P.R.]; Finnish Medical Foundation [to J.T.R.]; Emil Aaltonen Foundation [to J.T.R. and P.R.]; Biomedicum Helsinki Foundation [to J.T.R.]; Paulo Foundation [to J.T.R.]; Idman Foundation [to J.T.R.]; Veritas Foundation [to J.T.R.]; FIMM-EMBL PhD Fellowship grant [to S.H.]. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and nine industry partners (AbbVie, AstraZeneca, Biogen, Celgene, Genentech, GSK, Merck, Pfizer and Sanofi). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
AB - Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
UR - http://www.scopus.com/inward/record.url?scp=85072599380&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11954-8
DO - 10.1038/s41467-019-11954-8
M3 - Article
C2 - 31551469
AN - SCOPUS:85072599380
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4329
ER -