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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11954-8

2041-1723

Rubina Tabassum, Joel Rämö, Pietari Ripatti, Jukka Koskela, Mitja Kurki, Juha Karjalainen, Priit Palta, Shabbeer Hassan, Javier Núñez-Fontarnau, Tuomo Kiiskinen, Sanni Söderlund, Niina Matikainen, Mathias J. Gerl, Michał A. Surma, Christian Klose, Nathan O. Stitziel, Hannele Laivuori, Aki S. Havulinna, Susan K. Service, Veikko Salomaa, Matti Pirinen, Anu Jalanko, Jaakko Kaprio, Kati Donner, Mari Kaunisto, Nina Mars, Alexander Dada, Anastasia Shcherban, Andrea Ganna, Arto Lehistö, Elina Kilpeläinen, Georg Brein, Awaisa Ghazal, Jarmo Harju, Kalle Pärn, Pietro Della Briotta Parolo, Risto Kajanne, Susanna Lemmelä, Timo P. Sipilä, Tuomas Sipilä, Ulrike Lyhs, Vincent Llorens, Teemu Niiranen, Kati Kristiansson, Lotta Männikkö, Manuel González Jiménez, Markus Perola, Regis Wong, Terhi Kilpi, Tero Hiekkalinna, Elina Järvensivu, Essi Kaiharju, Hannele Mattsson, Markku Laukkanen, Päivi Laiho, Sini Lähteenmäki, Tuuli Sistonen, Sirpa Soini, Adam Ziemann, Anne Lehtonen, Apinya Lertratanakul, Bob Georgantas, Bridget Riley‐Gillis, Danjuma Quarless, Fedik Rahimov, Graham Heap, Howard J. Jacob, Jeffrey F. Waring, J. Wade Davis, Nizar Smaoui, Relja Popovic, Sahar Esmaeeli, Jeff Waring, Athena Matakidou, Ben Challis, David A. Close, Slavé Petrovski, Antti Karlsson, Johanna Schleutker, Kari Pulkki, Petri Virolainen, Lila Kallio, Graham J. Mann, Sami Heikkinen, Veli‐Matti Kosma, Chia‐Yen Chen, Heiko Runz, Jiang Liu, Paola G. Bronson, Sally John, Sanni Lahdenperä, Susan Eaton, Wei Zhou, Minna Hendolin, Outi Tuovila, Raimo Pakkanen, Joseph Maranville, Keith Usiskin, Marla Hochfeld, Robert Plenge, Robert Yang, Shameek Biswas, Steven M. Greenberg, Eija K. Laakkonen, Juha Kononen, Juha Paloneva, Urho M. Kujala, Teijo Kuopio, Jari A. Laukkanen, Eeva Kangasniemi, Kimmo Savinainen, Reijo Laaksonen, Mikko Arvas, Jarmo Ritari, Jukka Partanen, Kati Hyvärinen, Tiina Wahlfors, Andrew S. Peterson, Danny Oh, Diana Chang, Edmond Teng, Erich C. Strauss, Geoff Kerchner, Hao Chen, Hubert Chen, Jennifer L. Schutzman, John A. Michon, Julie Hunkapiller, Mark I. McCarthy, Natalie Bowers, Tim Lu, Tushar Bhangale, David Pulford, Dawn Waterworth, Diptee Kulkarni, Fanli Xu, Jo Betts, Jorge Esparza Gordillo, Joshua Hoffman, Kirsi Auro, Linda McCarthy, Soumitra Ghosh, Meg Ehm, Kimmo Pitkänen, Tomi P. Mäkelä, Anu Loukola, Heikki Joensuu, Juha Sinisalo, Kari K. Eklund, Lauri A. Aaltonen, Martti Färkkilâ, Olli Carpén, Dirk S. Paul, Pentti Tienari, Terhi Ollila, Jaakko Tuomilehto, Tuomo J Meretoja, Anne Pitkäranta, Joni A. Turunen, Katariina Hannula-Jouppi, Sampsa Pikkarainen, Sanna Seitsonen, Miika Koskinen, Antti Palomäki, Juha O. Rinne, Kaj Metsärinne, Klaus Elenius, Laura Pirilä, Leena Koulu, Markku Voutilainen, Markus Juonala, Sirkku Peltonen, Vesa Aaltonen, Andrey Loboda, Anna Podgornaia, Aparna Chhibber, Audrey Y. Chu, Caroline S. Fox, Dorothée Diogo, Emily Holzinger, John D. Eicher, Padhraig Gormley, Vinay Mehta, Xulong Wang, Johannes Kettunen, Katri Pylkäs, Marita Kalaoja, Minna K. Karjalainen, Reetta Hinttala, Riitta Kaarteenaho, Seppo Vainio, Tuomo Mantere, Seppo Vainio, Anne M. Remes, Johanna Huhtakangas, Juhani Junttila, Kaisa Tasanen, Laura Huilaja, Marja Luodonpää, Nina Hautala, Peeter Karihtala, Saila Kauppila, Terttu Harju, Timo Blomster, Hilkka Soininen, Ilkka T. Harvima, Jussi Pihlajamäki, Kai Kaarniranta, Margit Pelkonen, Markku Laakso, Mikko Hiltunen, Mikko Kiviniemi, Oili Kaipiainen‐Seppänen, Päivi Auvinen, Reetta Kälviäinen, Valtteri Julkunen, Anders Mälarstig, Åsa K. Hedman, Catherine Marshall, Christopher D. Whelan, Heli Lehtonen, Jaakko Parkkinen, Kari Linden, Kirsi Kalpala, Melissa Miller, Nan Bing, Stefan McDonough, Xing Chen, Xinli Hu, Ying Wu, Annika Auranen, Airi Jussila, Hannele Uusitalo‐Järvinen, Hannu Kankaanranta, Hannu Uusitalo, Jukka Peltola, Mika Kähönen, Pia Isomäki, Tarja Laitinen, Teea Salmi, Anthony J. Muslin, Clarence Wang, Clément Chatelain, Ethan Xu, Franck Augé, Kathy Call, Kathy Klinger, Marika Crohns, Matthias Gossel, Kimmo Palin, Manuel A. Rivas, Harri Siirtola, Javier Gracia‐Tabuenca, Matti Jauhiainen, Mark J. Daly, Nelson B. Freimer, Aarno Palotie, Marja‐Riitta Taskinen, Kai Simons, Samuli Ripatti,

Diabetes, Cardiovascular Risks, and Lipoproteins

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.