Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Tabassum, Rubina; Ramo, Joel T.; Ripatti, Pietari; Koskela, Jukka T.; Kurki, Mitja; Karjalainen, Juha; Palta, Priit; Hassan, Shabbeer; Nunez-Fontarnau, Javier; Kiiskinen, Tuomo T. J.; Soderlund, Sanni; Matikainen, Niina; Gerl, Mathias J.; Surma, Michal A.; Klose, Christian; Stitziel, Nathan O.; Laivuori, Hannele; Havulinna, Aki S.; Service, Susan K.; Salomaa, Veikko; Pirinen, Matti; Jauhiainen, Matti; Daly, Mark J.; Freimer, Nelson B.; Palotie, Aarno; Taskinen, Marja-Riitta; Simons, Kai; Ripatti, Samuli; Jalanko, Anu; Kaprio, Jaakko; Donner, Kati; Kaunisto, Mari; Mars, Nina; Dada, Alexander; Shcherban, Anastasia; Ganna, Andrea; Lehisto, Arto; Kilpelainen, Elina; Brein, Georg; Awaisa, Ghazal; Harju, Jarmo; Parr, Kalle; Parolo, Pietro Della Briotta; Kajanne, Risto; Lemmela, Susanna; Sipila, Timo P.; Sipila, Tuomas; Lyhs, Ulrike; Llorens, Vincent; Niiranen, Teemu; Kristiansson, Kati; Mannikko, Lotta; Jimenez, Manuel Gonzalez; Perola, Markus; Wong, Regis; Kilpi, Terhi; Hiekkalinna, Tero; Jarvensivu, Elina; Kaiharju, Essi; Mattsson, Hannele; Laukkanen, Markku; Laiho, Paivi; Lahteenmaki, Sini; Sistonen, Tuuli; Soini, Sirpa; Ziemann, Adam; Lehtonen, Anne; Lertratanakul, Apinya; Georgantas, Bob; Riley-Gillis, Bridget; Quarless, Danjuma; Rahimov, Fedik; Heap, Graham; Jacob, Howard; Waring, Jeffrey; Davis, Justin Wade; Smaoui, Nizar; Popovic, Relja; Esmaeeli, Sahar; Waring, Jeff; Matakidou, Athena; Challis, Ben; Close, David; Petrovski, Slave; Karlsson, Antti; Schleutker, Johanna; Pulkki, Kari; Virolainen, Petri; Kallio, Lila; Mannermaa, Arto; Heikkinen, Sami; Kosma, Veli-Matti; Chen, Chia-Yen; Runz, Heiko; Liu, Jimmy; Bronson, Paola; John, Sally; Landenpera, Sanni; Eaton, Susan; Zhou, Wei; Hendolin, Minna; Tuovila, Outi; Pakkanen, Raimo; Maranville, Joseph; Usiskin, Keith; Hochfeld, Marla; Plenge, Robert; Yang, Robert; Biswas, Shameek; Greenberg, Steven; Laakkonen, Eija; Kononen, Juha; Paloneva, Juha; Kujala, Urho; Kuopio, Teijo; Laukkanen, Jari; Kangasniemi, Eeva; Savinainen, Kimmo; Laaksonen, Reijo; Arvas, Mikko; Ritari, Jarmo; Partanen, Jukka; Hyvarinen, Kati; Wahlfors, Tiina; Peterson, Andrew; Oh, Danny; Chang, Diana; Teng, Edmond; Strauss, Erich; Kerchner, Geoff; Chen, Hao; Chen, Hubert; Schutzman, Jennifer; Michon, John; Hunkapiller, Julie; McCarthy, Mark; Bowers, Natalie; Lu, Tim; Bhangale, Tushar; Pulford, David; Waterworth, Dawn; Kulkarni, Diptee; Xu, Fanli; Betts, Jo; Gordillo, Jorge Esparza; Hoffman, Joshua; Auro, Kirsi; McCarthy, Linda; Ghosh, Soumitra; Ehm, Meg; Pitkanen, Kimmo; Makela, Tomi; Loukola, Anu; Joensuu, Heikki; Sinisalo, Juha; Eklund, Kari; Aaltonen, Lauri; Farkkila, Martti; Carpen, Olli; Kauppi, Paula; Tienari, Pentti; Ollila, Terhi; Tuomi, Tiinamaija; Meretoja, Tuomo; Pitkaranta, Anne; Turunen, Joni; Hannula-Jouppi, Katariina; Pikkarainen, Sampsa; Seitsonen, Sanna; Koskinen, Miika; Palomaki, Antti; Rinne, Juha; Metsarinne, Kaj; Elenius, Klaus; Pirila, Laura; Koulu, Leena; Voutilainen, Markku; Juonala, Markus; Peltonen, Sirkku; Aaltonen, Vesa; Loboda, Andrey; Podgornaia, Anna; Chhibber, Aparna; Chu, Audrey; Fox, Caroline; Diogo, Dorothee; Holzinger, Emily; Eicher, John; Gormley, Padhraig; Mehta, Vinay; Wang, Xulong; Kettunen, Johannes; Pylkas, Katri; Kalaoja, Marita; Karjalainen, Minna; Hinttala, Reetta; Kaarteenaho, Riitta; Vainio, Seppo; Mantere, Tuomo; Remes, Anne; Huhtakangas, Johanna; Junttila, Juhani; Tasanen, Kaisa; Huilaja, Laura; Luodonpaa, Marja; Hautala, Nina; Karihtala, Peeter; Kauppila, Saila; Harju, Terttu; Blomster, Timo; Soininen, Hilkka; Harvima, Ilkka; Pihlajamaki, Jussi; Kaarniranta, Kai; Pelkonen, Margit; Laakso, Markku; Hiltunen, Mikko; Kiviniemi, Mikko; Kaipiainen-Seppanen, Oili; Auvinen, Paivi; Kalviainen, Reetta; Julkunen, Valtteri; Malarstig, Anders; Hedman, Asa; Marshal, Catherine; Whelan, Christopher; Lehtonen, Heli; Parkkinen, Jaakko; Linden, Kari; Kalpala, Kirsi; Miller, Melissa; Bing, Nan; McDonough, Stefan; Chen, Xing; Hu, Xinli; Wu, Ying; Auranen, Annika; Jussila, Airi; Uusitalo-Jarvinen, Hannele; Kankaanranta, Hannu; Uusitalo, Hannu; Peltola, Jukka; Kahonen, Mika; Isomaki, Pia; Laitinen, Tarja; Salmi, Teea; Muslin, Anthony; Wang, Clarence; Chatelain, Clement; Xu, Ethan; Auge, Franck; Call, Kathy; Klinger, Kathy; Crohns, Marika; Gossel, Matthias; Palin, Kimmo; Rivas, Manuel; Siirtola, Harri; Tabuenca, Javier Gracia (2019-09-24)
Springer Nature
24.09.2019
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
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© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe202003127981
https://urn.fi/URN:NBN:fi-fe202003127981
Tiivistelmä
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.
Kokoelmat
- Avoin saatavuus [34166]
Ellei muuten mainita, aineiston lisenssi on https://creativecommons.org/licenses/by/4.0/