Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Rubina Tabassum(University of Helsinki), Joel Rämö(University of Helsinki), Pietari Ripatti(University of Helsinki), Jukka Koskela(University of Helsinki), Mitja Kurki(Broad Institute), Juha Karjalainen(Broad Institute), Priit Palta(University of Helsinki), Shabbeer Hassan(University of Helsinki), Javier Núñez-Fontarnau(University of Helsinki), Tuomo Kiiskinen(University of Helsinki), Sanni Söderlund(University of Helsinki), Niina Matikainen(University of Helsinki), Mathias J. Gerl, Michał A. Surma(Łukasiewicz Research Network – PORT Polish Center for Technology Development), Christian Klose, Nathan O. Stitziel(James S. McDonnell Foundation), Hannele Laivuori(University of Helsinki), Aki S. Havulinna(University of Helsinki), Susan K. Service(University of California, Los Angeles), Veikko Salomaa(Finnish Institute for Health and Welfare), Matti Pirinen(University of Helsinki), FinnGen Project(University of Helsinki), Anu Jalanko(University of Helsinki), Jaakko Kaprio(University of Helsinki), Kati Donner(University of Helsinki), Mari Kaunisto(University of Helsinki), Nina Mars(University of Helsinki), Alexander Dada(University of Helsinki), Anastasia Shcherban(University of Helsinki), Andrea Ganna(University of Helsinki), Arto Lehistö(University of Helsinki), Elina Kilpeläinen(University of Helsinki), Georg Brein(University of Helsinki), Awaisa Ghazal(University of Helsinki), Jarmo Harju(University of Helsinki), Kalle Pärn(University of Helsinki), Pietro Della Briotta Parolo(University of Helsinki), Risto Kajanne(University of Helsinki), Susanna Lemmelä(University of Helsinki), Timo P. Sipilä(University of Helsinki), Tuomas Sipilä(University of Helsinki), Ulrike Lyhs(University of Helsinki), Vincent Llorens(University of Helsinki), Teemu Niiranen(Finnish Institute for Health and Welfare), Kati Kristiansson(Finnish Institute for Health and Welfare), Lotta Männikkö(Finnish Institute for Health and Welfare), Manuel González Jiménez(Finnish Institute for Health and Welfare), Markus Perola(Finnish Institute for Health and Welfare), Regis Wong(Finnish Institute for Health and Welfare), Terhi Kilpi(Finnish Institute for Health and Welfare), Tero Hiekkalinna(Finnish Institute for Health and Welfare), Elina Järvensivu(Finnish Institute for Health and Welfare), Essi Kaiharju(Finnish Institute for Health and Welfare), Hannele Mattsson(Finnish Institute for Health and Welfare), Markku Laukkanen(Finnish Institute for Health and Welfare), Päivi Laiho(Finnish Institute for Health and Welfare), Sini Lähteenmäki(Finnish Institute for Health and Welfare), Tuuli Sistonen(Finnish Institute for Health and Welfare), Sirpa Soini(AbbVie (United States)), Adam Ziemann(AbbVie (United States)), Anne Lehtonen(AbbVie (United States)), Apinya Lertratanakul(AbbVie (United States)), Bob Georgantas(AbbVie (United States)), Bridget Riley‐Gillis(AbbVie (United States)), Danjuma Quarless(AbbVie (United States)), Fedik Rahimov(AbbVie (United States)), Graham Heap(AbbVie (United States)), Howard J. Jacob(AbbVie (United States)), Jeffrey F. Waring(AbbVie (United States)), J. Wade Davis(AbbVie (United States)), Nizar Smaoui(AbbVie (United States)), Relja Popovic(AbbVie (United States)), Sahar Esmaeeli(AbbVie (United States)), Jeff Waring(AstraZeneca (United Kingdom)), Athena Matakidou(AstraZeneca (United Kingdom)), Ben Challis(AstraZeneca (United Kingdom)), David A. Close(AstraZeneca (United Kingdom)), Slavé Petrovski(AstraZeneca (United Kingdom)), Antti Karlsson(University of Turku), Johanna Schleutker(University of Turku), Kari Pulkki(University of Turku), Petri Virolainen(University of Turku), Lila Kallio(University of Eastern Finland), Arto Mannermaa(University of Eastern Finland), Sami Heikkinen(University of Eastern Finland), Veli‐Matti Kosma(Biogen (United States)), Chia‐Yen Chen(Biogen (United States)), Heiko Runz(Biogen (United States)), Jimmy Liu(Biogen (United States)), Paola G. Bronson(Biogen (United States)), Sally John(Biogen (United States)), Sanni Lahdenperä(Biogen (United States)), Susan Eaton(Broad Institute), Wei Zhou(Broad Institute), Minna Hendolin(Business Finland), Outi Tuovila(Business Finland), Raimo Pakkanen(Business Finland), Joseph Maranville, Keith Usiskin, Marla Hochfeld, Robert M. Plenge, Robert Yang, Shameek Biswas, Steven M. Greenberg(Central Finland Health Care District), Eija K. Laakkonen(Central Finland Health Care District), Juha Kononen(Central Finland Health Care District), Juha Paloneva(Central Finland Health Care District), Urho M. Kujala(Central Finland Health Care District), Teijo Kuopio(Central Finland Health Care District), Jari A. Laukkanen(Tampere University), Eeva Kangasniemi(Tampere University), Kimmo Savinainen(Tampere University), Reijo Laaksonen(Tampere University), Mikko Arvas(Finnish Red Cross), Jarmo Ritari(Finnish Red Cross), Jukka Partanen(Finnish Red Cross), Kati Hyvärinen(Finnish Red Cross), Tiina Wahlfors(Finnish Red Cross), 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(GlaxoSmithKline (United Kingdom)), David Pulford(GlaxoSmithKline (United Kingdom)), Dawn Waterworth(GlaxoSmithKline (United Kingdom)), Diptee Kulkarni(GlaxoSmithKline (United Kingdom)), Fanli Xu(GlaxoSmithKline (United Kingdom)), Jo Betts(GlaxoSmithKline (United Kingdom)), Jorge Esparza Gordillo(GlaxoSmithKline (United Kingdom)), Joshua Hoffman(GlaxoSmithKline (United Kingdom)), Kirsi Auro(GlaxoSmithKline (United Kingdom)), Linda McCarthy(GlaxoSmithKline (United Kingdom)), Soumitra Ghosh(GlaxoSmithKline (United Kingdom)), Meg Ehm(GlaxoSmithKline (United Kingdom)), Kimmo Pitkänen(University of Helsinki), Tomi P. Mäkelä(University of Helsinki), Anu Loukola(Hospital District of Helsinki and Uusimaa), Heikki Joensuu(Hospital District of Helsinki and Uusimaa), Juha Sinisalo(Hospital District of Helsinki and Uusimaa), Kari K. Eklund(Hospital District of Helsinki and Uusimaa), Lauri A. Aaltonen(Hospital District of Helsinki and Uusimaa), Martti Färkkilâ(Hospital District of Helsinki and Uusimaa), Olli Carpén(Hospital District of Helsinki and Uusimaa), Paula Kauppi(Hospital District of Helsinki and Uusimaa), Pentti Tienari(Hospital District of Helsinki and Uusimaa), Terhi Ollila(Hospital District of Helsinki and Uusimaa), Tiinamaija Tuomi(Hospital District of Helsinki and Uusimaa), Tuomo J Meretoja(Hospital District of Helsinki and Uusimaa), Anne Pitkäranta(Hospital District of Helsinki and Uusimaa), Joni A. Turunen(Hospital District of Helsinki and Uusimaa), Katariina Hannula‐Jouppi(Hospital District of Helsinki and Uusimaa), Sampsa Pikkarainen(Hospital District of Helsinki and Uusimaa), Sanna Seitsonen(Hospital District of Helsinki and Uusimaa), Miika Koskinen(Varsinais-Suomen Sairaanhoitopiiri), Antti Palomäki(Varsinais-Suomen Sairaanhoitopiiri), Juha O. Rinne(Varsinais-Suomen Sairaanhoitopiiri), Kaj Metsärinne(Varsinais-Suomen Sairaanhoitopiiri), Klaus Elenius(Varsinais-Suomen Sairaanhoitopiiri), Laura Pirilä(Varsinais-Suomen Sairaanhoitopiiri), Leena Koulu(Varsinais-Suomen Sairaanhoitopiiri), Markku Voutilainen(Varsinais-Suomen Sairaanhoitopiiri), Markus Juonala(Varsinais-Suomen Sairaanhoitopiiri), Sirkku Peltonen(Varsinais-Suomen Sairaanhoitopiiri), Vesa Aaltonen(Merck & Co., Inc., Rahway, NJ, USA (United States)), Andrey Loboda(Merck & Co., Inc., Rahway, NJ, USA (United States)), Anna Podgornaia(Merck & Co., Inc., Rahway, NJ, USA (United States)), Aparna Chhibber(Merck & Co., Inc., Rahway, NJ, USA (United States)), Audrey Y. Chu(Merck & Co., Inc., Rahway, NJ, USA (United States)), Caroline S. Fox(Merck & Co., Inc., Rahway, NJ, USA (United States)), Dorothée Diogo(Merck & Co., Inc., Rahway, NJ, USA (United States)), Emily Holzinger(Merck & Co., Inc., Rahway, NJ, USA (United States)), John D. Eicher(Merck & Co., Inc., Rahway, NJ, USA (United States)), Padhraig Gormley(Merck & Co., Inc., Rahway, NJ, USA (United States)), Vinay Mehta(Merck & Co., Inc., Rahway, NJ, USA (United States)), Xulong Wang(Merck & Co., Inc., Rahway, NJ, USA (United States)), Johannes Kettunen(Borealis (Finland)), Katri Pylkäs(Borealis (Finland)), Marita Kalaoja(Borealis (Finland)), Minna K. Karjalainen(Borealis (Finland)), Reetta Hinttala(Borealis (Finland)), Riitta Kaarteenaho(Borealis (Finland)), Seppo Vainio(Borealis (Finland)), Tuomo Mantere(Borealis (Finland)), Seppo Vainio(Borealis (Finland)), Anne M. Remes(Northern Ostrobothnia Hospital District), Johanna Huhtakangas(Northern Ostrobothnia Hospital District), Juhani Junttila(Northern Ostrobothnia Hospital District), Kaisa Tasanen(Northern Ostrobothnia Hospital District), Laura Huilaja(Northern Ostrobothnia Hospital District), Marja Luodonpää(Northern Ostrobothnia Hospital District), Nina Hautala(Northern Ostrobothnia Hospital District), Peeter Karihtala(Northern Ostrobothnia Hospital District), Saila Kauppila(Northern Ostrobothnia Hospital District), Terttu Harju(Northern Ostrobothnia Hospital District), Timo Blomster(Northern Ostrobothnia Hospital District), 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(Pfizer (United States)), Anders Mälarstig(Pfizer (United States)), Åsa K. Hedman(Pfizer (United States)), Catherine Marshall(Pfizer (United States)), Christopher D. Whelan(Pfizer (United States)), Heli Lehtonen(Pfizer (United States)), Jaakko Parkkinen(Pfizer (United States)), Kari Linden(Pfizer (United States)), Kirsi Kalpala(Pfizer (United States)), Melissa Miller(Pfizer (United States)), Nan Bing(Pfizer (United States)), Stefan McDonough(Pfizer (United States)), Xing Chen(Pfizer (United States)), Xinli Hu(Pfizer (United States)), Ying Wu(Pfizer (United States)), Annika Auranen(Pirkanmaa Hospital District), Airi Jussila(Pirkanmaa Hospital District), Hannele Uusitalo‐Järvinen(Pirkanmaa Hospital District), Hannu Kankaanranta(Pirkanmaa Hospital District), Hannu Uusitalo(Pirkanmaa Hospital District), Jukka Peltola(Pirkanmaa Hospital District), Mika Kähönen(Pirkanmaa Hospital District), Pia Isomäki(Pirkanmaa Hospital District), Tarja Laitinen(Pirkanmaa Hospital District), Teea Salmi(Sanofi (France)), Anthony J. Muslin(Sanofi (France)), Clarence Wang(Sanofi (France)), Clément Chatelain(Sanofi (France)), Ethan Xu(Sanofi (France)), Franck Augé(Sanofi (France)), Kathy Call(Sanofi (France)), Kathy Klinger(Sanofi (France)), Marika Crohns(Sanofi (France)), Matthias Gossel(University of Helsinki), Kimmo Palin(University of Helsinki), Manuel A. Rivas(Tampere University), Harri Siirtola(Tampere University), Javier Gracia‐Tabuenca(Tampere University), Matti Jauhiainen(Broad Institute), Mark J. Daly(Broad Institute), Nelson B. Freimer(University of California, Los Angeles), Aarno Palotie(Broad Institute), Marja‐Riitta Taskinen(University of Helsinki), Kai Simons(University of Helsinki), Samuli Ripatti(Broad Institute)
Cited by 194Open Access
Abstract
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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