University of Oulu

Tabassum, R., Rämö, J.T., Ripatti, P. et al. Genetic architecture of human plasma lipidome and its link to cardiovascular disease. Nat Commun 10, 4329 (2019). https://doi.org/10.1038/s41467-019-11954-8

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

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Author: Tabassum, Rubina1; Ramo, Joel T.1; Ripatti, Pietari1;
Koskela, Jukka T.1; Kurki, Mitja1,2,3; Karjalainen, Juha1,4,5,6; Palta, Priit1,7; Hassan, Shabbeer1; Nunez-Fontarnau, Javier1; Kiiskinen, Tuomo T. J.1,8; Soderlund, Sanni9,10; Matikainen, Niina9,10,11; Gerl, Mathias J.12; Surma, Michal A.12,13; Klose, Christian12; Stitziel, Nathan O.14,15,16; Laivuori, Hannele1,17,18,19,20; Havulinna, Aki S.1,8; Service, Susan K.21; Salomaa, Veikko8; Pirinen, Matti1,22,23,24; Jauhiainen, Matti8,25; Daly, Mark J.1,4; Freimer, Nelson B.21; Palotie, Aarno1,4,26,27; Taskinen, Marja-Riitta9,10; Simons, Kai12,28; Ripatti, Samuli1,4,29; Jalanko, Anu1; Kaprio, Jaakko1; Donner, Kati1; Kaunisto, Mari1; Mars, Nina1; Dada, Alexander1; Shcherban, Anastasia1; Ganna, Andrea1; Lehisto, Arto1; Kilpelainen, Elina1; Brein, Georg1; Awaisa, Ghazal1; Harju, Jarmo1; Parr, Kalle1; Parolo, Pietro Della Briotta1; Kajanne, Risto1; Lemmela, Susanna1; Sipila, Timo P.1; Sipila, Tuomas1; Lyhs, Ulrike1; Llorens, Vincent1; Niiranen, Teemu8; Kristiansson, Kati8; Mannikko, Lotta8; Jimenez, Manuel Gonzalez8; Perola, Markus8; Wong, Regis8; Kilpi, Terhi8; Hiekkalinna, Tero8; Jarvensivu, Elina8; Kaiharju, Essi8; Mattsson, Hannele8; Laukkanen, Markku8; Laiho, Paivi8; Lahteenmaki, Sini8; Sistonen, Tuuli8; Soini, Sirpa8; Ziemann, Adam30; Lehtonen, Anne30; Lertratanakul, Apinya30; Georgantas, Bob30; Riley-Gillis, Bridget30; Quarless, Danjuma30; Rahimov, Fedik30; Heap, Graham30; Jacob, Howard30; Waring, Jeffrey30; Davis, Justin Wade30; Smaoui, Nizar30; Popovic, Relja30; Esmaeeli, Sahar30; Waring, Jeff30; Matakidou, Athena31; Challis, Ben31; Close, David31; Petrovski, Slave31; Karlsson, Antti32,33; Schleutker, Johanna32,33; Pulkki, Kari32,33; Virolainen, Petri32,33; Kallio, Lila34; Mannermaa, Arto35,36; Heikkinen, Sami35,36; Kosma, Veli-Matti37; Chen, Chia-Yen38; Runz, Heiko38; Liu, Jimmy38; Bronson, Paola38; John, Sally38; Landenpera, Sanni38; Eaton, Susan38; Zhou, Wei4; Hendolin, Minna39; Tuovila, Outi39; Pakkanen, Raimo39; Maranville, Joseph40; Usiskin, Keith40; Hochfeld, Marla40; Plenge, Robert40; Yang, Robert40; Biswas, Shameek40; Greenberg, Steven40; Laakkonen, Eija41,42; Kononen, Juha41,42; Paloneva, Juha41,42; Kujala, Urho41,42; Kuopio, Teijo43; Laukkanen, Jari42; Kangasniemi, Eeva44,45; Savinainen, Kimmo44,45; Laaksonen, Reijo44,45; Arvas, Mikko46,47,48; Ritari, Jarmo46,47,48; Partanen, Jukka46,47,48; Hyvarinen, Kati46,47,48; Wahlfors, Tiina46,47,48; Peterson, Andrew49; Oh, Danny49; Chang, Diana49; Teng, Edmond49; Strauss, Erich49; Kerchner, Geoff49; Chen, Hao49; Chen, Hubert49; Schutzman, Jennifer49; Michon, John49; Hunkapiller, Julie49; McCarthy, Mark49; Bowers, Natalie49; Lu, Tim49; Bhangale, Tushar49; Pulford, David50; Waterworth, Dawn50; Kulkarni, Diptee50; Xu, Fanli50; Betts, Jo50; Gordillo, Jorge Esparza50; Hoffman, Joshua50; Auro, Kirsi50; McCarthy, Linda50; Ghosh, Soumitra50; Ehm, Meg50; Pitkanen, Kimmo51; Makela, Tomi52; Loukola, Anu53; Joensuu, Heikki53; Sinisalo, Juha53; Eklund, Kari53; Aaltonen, Lauri53; Farkkila, Martti53; Carpen, Olli53; Kauppi, Paula53; Tienari, Pentti53; Ollila, Terhi53; Tuomi, Tiinamaija53; Meretoja, Tuomo53; Pitkaranta, Anne53; Turunen, Joni53; Hannula-Jouppi, Katariina53; Pikkarainen, Sampsa53; Seitsonen, Sanna53; Koskinen, Miika53; Palomaki, Antti33; Rinne, Juha33; Metsarinne, Kaj33; Elenius, Klaus33; Pirila, Laura33; Koulu, Leena33; Voutilainen, Markku33; Juonala, Markus33; Peltonen, Sirkku33; Aaltonen, Vesa33; Loboda, Andrey54; Podgornaia, Anna54; Chhibber, Aparna54; Chu, Audrey54; Fox, Caroline54; Diogo, Dorothee54; Holzinger, Emily54; Eicher, John54; Gormley, Padhraig54; Mehta, Vinay54; Wang, Xulong54; Kettunen, Johannes55,56; Pylkas, Katri55,56; Kalaoja, Marita55,56; Karjalainen, Minna55,56; Hinttala, Reetta55,56; Kaarteenaho, Riitta55,56; Vainio, Seppo55,56,57; Mantere, Tuomo55,56; Remes, Anne56; Huhtakangas, Johanna56; Junttila, Juhani56; Tasanen, Kaisa56; Huilaja, Laura56; Luodonpaa, Marja56; Hautala, Nina56; Karihtala, Peeter56; Kauppila, Saila56; Harju, Terttu56; Blomster, Timo56; Soininen, Hilkka36; Harvima, Ilkka36; Pihlajamaki, Jussi36; Kaarniranta, Kai36; Pelkonen, Margit36; Laakso, Markku36; Hiltunen, Mikko36; Kiviniemi, Mikko36; Kaipiainen-Seppanen, Oili36; Auvinen, Paivi36; Kalviainen, Reetta36; Julkunen, Valtteri36; Malarstig, Anders58; Hedman, Asa58; Marshal, Catherine58; Whelan, Christopher58; Lehtonen, Heli58; Parkkinen, Jaakko58; Linden, Kari58; Kalpala, Kirsi58; Miller, Melissa58; Bing, Nan58; McDonough, Stefan58; Chen, Xing58; Hu, Xinli58; Wu, Ying58; Auranen, Annika45; Jussila, Airi45; Uusitalo-Jarvinen, Hannele45; Kankaanranta, Hannu45; Uusitalo, Hannu45; Peltola, Jukka45; Kahonen, Mika45; Isomaki, Pia45; Laitinen, Tarja45; Salmi, Teea45; Muslin, Anthony59; Wang, Clarence59; Chatelain, Clement59; Xu, Ethan59; Auge, Franck59; Call, Kathy59; Klinger, Kathy59; Crohns, Marika59; Gossel, Matthias59; Palin, Kimmo60; Rivas, Manuel61; Siirtola, Harri62; Tabuenca, Javier Gracia62
Organizations: 1Univ Helsinki, HiLIFE, Inst Mol Med Finland, Helsinki, Finland.
2Broad Inst MIT & Harvard, Program Med & Populat Genet & Genet Anal Platform, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
3Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
4Broad Inst MIT & Harvard Univ, Cambridge, MA 02142 USA.
5Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
6Harvard Med Sch, Boston, MA 02115 USA.
7Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
8Natl Inst Hlth & Welf, Helsinki, Finland.
9Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.
10Helsinki Univ Hosp, Dept Internal Med, Helsinki, Finland.
11Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland.
12Lipotype GmbH, Dresden, Germany.
13Port Polish Ctr Technol Dev, Lukasiewicz Res Network, Stablowicka 147 Str, PL-54066 Wroclaw, Poland.
14Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
15Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
16Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA.
17Tampere Univ Hosp, Dept Obstet & Gynecol, Tampere, Finland.
18Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland.
19Univ Helsinki, Med & Clin Genet, Helsinki, Finland.
20Helsinki Univ Hosp, Helsinki, Finland.
21Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA.
22Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
23Univ Helsinki, HIIT, Helsinki, Finland.
24Univ Helsinki, Dept Math & Stat, Helsinki, Finland.
25Minerva Fdn, Biomed, Helsinki, Finland.
26Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Dept Psychiat, Analyt & Translat Genet Unit,Dept Med, Boston, MA 02114 USA.
27Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
28Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany.
29Univ Helsinki, Fac Med, Dept Publ Hlth, Clinicum, Helsinki, Finland.
30Abbvie, Chicago, IL 60064 USA.
31Astra Zeneca, Cambridge, England.
32Univ Turku, Auria Biobank, Turku, Finland.
33Hosp Dist Southwest Finland, Turku, Finland.
34Auria Biobank, Turku, Finland.
35Univ Eastern Finland, Biobank Eastern Finland, Kuopio, Finland.
36Northern Savo Hosp Dist, Kuopio, Finland.
37Biobank Eastern Finland, Kuopio, Finland.
38Biogen, Cambridge, MA USA.
39Business Finland, Helsinki, Finland.
40Celgene, Summit, NJ USA.
41Univ Jyvaskyla, Cent Finland Biobank, Jyvaskyla, Finland.
42Cent Finland Hlth Care Dist, Jyvaskyla, Finland.
43Cent Finland Biobank, Jyvaskyla, Finland.
44Univ Tampere, Finnish Clin Biobank Tampere, Tampere, Finland.
45Pirkanmaa Hosp Dist, Tampere, Finland.
46Finnish Red Cross Blood Serv, Helsinki, Finland.
47Finnish Hematol Registry, Helsinki, Finland.
48Clin Biobank, Helsinki, Finland.
49Genentech Inc, San Francisco, CA USA.
50GlaxoSmithKline, Brentford, England.
51Helsinki Biobank, Helsinki, Finland.
52Univ Helsinki, HiLIFE, Helsinki, Finland.
53Hosp Dist Helsinki & Uusimaa, Helsinki, Finland.
54Merck, Kenilworth, NJ USA.
55Univ Oulu, Northern Finland Biobank Borealis, Oulu, Finland.
56Northern Ostrobothnia Hosp Dist, Oulu, Finland.
57Northern Finland Biobank Borealis, Oulu, Finland.
58Pfizer, New York, NY USA.
59Sanofi, Paris, France.
60Univ Helsinki, Helsinki, Finland.
61Univ Stanford, Stanford, CA USA.
62Univ Tampere, Tampere, Finland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202003127981
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-03-12
Description:

Abstract

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.

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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 10
Issue: 1
Article number: 4329
DOI: 10.1038/s41467-019-11954-8
OADOI: https://oadoi.org/10.1038/s41467-019-11954-8
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
Subjects:
Funding: 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.
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