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
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042823334
https://urn.fi/URN:NBN:fi-fe2021042823334
Tiivistelmä
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.
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