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




Tabassum R, Ramo JT, Ripatti P, Koskela JT, Kurki M, Karjalainen J, Palta P, Hassan S, Nunez-Fontarnau J, Kiiskinen TTJ, Soderlund S, Matikainen N, Gerl MJ, Surma MA, Klose C, Stitziel NO, Laivuori H, Havulinna AS, Service SK, Salomaa V, Pirinen M, Jauhiainen M, Daly MJ, Freimer NB, Palotie A, Taskinen MR, Simons K, Ripatti S, Jalanko A, Kaprio J, Donner K, Kaunisto M, Mars N, Dada A, Shcherban A, Ganna A, Lehisto A, Kilpelainen E, Brein G, Awaisa G, Harju J, Parr K, Parolo PD, Kajanne R, Lemmela S, Sipila TP, Sipila T, Lyhs U, Llorens V, Niiranen T, Kristiansson K, Mannikko L, Jimenez MG, Perola M, Wong R, Kilpi T, Hiekkalinna T, Jarvensivu E, Kaiharju E, Mattsson H, Laukkanen M, Laiho P, Lahteenmaki S, Sistonen T, Soini S, Ziemann A, Lehtonen A, Lertratanakul A, Georgantas B, Riley-Gillis B, Quarless D, Rahimov F, Heap G, Jacob H, Waring J, Davis JW, Smaoui N, Popovic R, Esmaeeli S, Waring J, Matakidou A, Challis B, Close D, Petrovski S, Karlsson A, Schleutker J, Pulkki K, Virolainen P, Kallio L, Mannermaa A, Heikkinen S, Kosma VM, Chen CY, Runz H, Liu J, Bronson P, John S, Landenpera S, Eaton S, Zhou W, Hendolin M, Tuovila O, Pakkanen R, Maranville J, Usiskin K, Hochfeld M, Plenge R, Yang R, Biswas S, Greenberg S, Laakkonen E, Kononen J, Paloneva J, Kujala U, Kuopio T, Laukkanen J, Kangasniemi E, Savinainen K, Laaksonen R, Arvas M, Ritari J, Partanen J, Hyvarinen K, Wahlfors T, Peterson A, Oh D, Chang D, Teng E, Strauss E, Kerchner G, Chen H, Chen H, Schutzman J, Michon J, Hunkapiller J, McCarthy M, Bowers N, Lu T, Bhangale T, Pulford D, Waterworth D, Kulkarni D, Xu FL, Betts J, Gordillo JE, Hoffman J, Auro K, McCarthy L, Ghosh S, Ehm M, Pitkanen K, Makela T, Loukola A, Joensuu H, Sinisalo J, Eklund K, Aaltonen L, Farkkila M, Carpen O, Kauppi P, Tienari P, Ollila T, Tuomi T, Meretoja T, Pitkaranta A, Turunen J, Hannula-Jouppi K, Pikkarainen S, Seitsonen S, Koskinen M, Palomaki A, Rinne J, Metsarinne K, Elenius K, Pirila L, Koulu L, Voutilainen M, Juonala M, Peltonen S, Aaltonen V, Loboda A, Podgornaia A, Chhibber A, Chu A, Fox C, Diogo D, Holzinger E, Eicher J, Gormley P, Mehta V, Wang XL, Kettunen J, Pylkas K, Kalaoja M, Karjalainen M, Hinttala R, Kaarteenaho R, Vainio S, Mantere T, Remes A, Huhtakangas J, Junttila J, Tasanen K, Huilaja L, Luodonpaa M, Hautala N, Karihtala P, Kauppila S, Harju T, Blomster T, Soininen H, Harvima I, Pihlajamaki J, Kaarniranta K, Pelkonen M, Laakso M, Hiltunen M, Kiviniemi M, Kaipiainen-Seppanen O, Auvinen P, Kalviainen R, Julkunen V, Malarstig A, Hedman A, Marshal C, Whelan C, Lehtonen H, Parkkinen J, Linden K, Kalpala K, Miller M, Bing N, McDonough S, Chen X, Hu XL, Wu Y, Auranen A, Jussila A, Uusitalo-Jarvinen H, Kankaanranta H, Uusitalo H, Peltola J, Kahonen M, Isomaki P, Laitinen T, Salmi T, Muslin A, Wang C, Chatelain C, Xu E, Auge F, Call K, Klinger K, Crohns M, Gossel M, Palin K, Rivas M, Siirtola H, Tabuenca JG

PublisherNATURE PUBLISHING GROUP

2019

Nature Communications

NATURE COMMUNICATIONS

NAT COMMUN

ARTN 4329

10

14

2041-1723

2041-1723

DOIhttps://doi.org/10.1038/s41467-019-11954-8

https://www.nature.com/articles/s41467-019-11954-8

https://research.utu.fi/converis/portal/detail/Publication/45110995



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 x10(-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.

Last updated on 2024-26-11 at 19:58