Biological, clinical and population relevance of 95 loci for blood lipids.

Teslovich, T.M.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Ripatti, S.; Chasman, D.I.; Willer, C.J.; Johansen, C.T.; Fouchier, S.W.; Isaacs, A.; Peloso, G.M.; Barbalic, M.; Ricketts, S.L.; Bis, J.C.; Aulchenko, Y.S.; Thorleifsson, G.; Feitosa, M.F.; Chambers, J.; Orho-Melander, M.; Melander, O.; Johnson, T.; Li, X.; Guo, X.; Li, M.; Shin Cho, Y.; Jin Go, M.; Jin Kim, Y.; Lee, J.Y.; Park, T.; Kim, K.; Sim, X.; Twee-Hee Ong, R.; Croteau-Chonka, D.C.; Lange, L.A.; Smith, J.D.; Song, K.; Hua Zhao, J.; Yuan, X.; Luan, J.; Lamina, C.; Ziegler, A.; Zhang, W.; Zee, R.Y.; Wright, A.F.; Witteman, J.C.; Wilson, J.F.; Willemsen, G.; Wichmann, H.E.; Whitfield, J.B.; Waterworth, D.M.; Wareham, N.J.; Waeber, G.; Vollenweider, P.; Voight, B.F.; Vitart, V.; Uitterlinden, A.G.; Uda, M.; Tuomilehto, J.; Thompson, J.R.; Tanaka, T.; Surakka, I.; Stringham, H.M.; Spector, T.D.; Soranzo, N.; Smit, J.H.; Sinisalo, J.; Silander, K.; Sijbrands, E.J.; Scuteri, A.; Scott, J.; Schlessinger, D.; Sanna, S.; Salomaa, V.; Saharinen, J.; Sabatti, C.; Ruokonen, A.; Rudan, I.; Rose, L.M.; Roberts, R.; Rieder, M.; Psaty, B.M.; Pramstaller, P.P.; Pichler, I.; Perola, M.; Penninx, B.W.; Pedersen, N.L.; Pattaro, C.; Parker, A.N.; Pare, G.; Oostra, B.A.; O'Donnell, C.J.; Nieminen, M.S.; Nickerson, D.A.; Montgomery, G.W.; Meitinger, T.; McPherson, R.; McCarthy, M.I.; McArdle, W.; Masson, D.; Martin, N.G.; Marroni, F.; Mangino, M.; Magnusson, P.K.; Lucas, G.; Luben, R.; Loos, R.J.; Lokki, M.L.; Lettre, G.; Langenberg, C.; Launer, L.J.; Lakatta, E.G.; Laaksonen, R.; Kyvik, K.O.; Kronenberg, F.; König, I.R.; Khaw, K.T.; Kaprio, J.; Kaplan, L.M.; Johansson, A.; Jarvelin, M.R.; Janssens, A.C.; Ingelsson, E.; Igl, W.; Kees Hovingh, G.; Hottenga, J.J.; Hofman, A.; Hicks, A.A.; Hengstenberg, C.; Heid, I.M.; Hayward, C.; Havulinna, A.S.; Hastie, N.D.; Harris, T.B.; Haritunians, T.; Hall, A.S.; Gyllensten, U.; Guiducci, C.; Groop, L.C.; Gonzalez, E.; Gieger, C.; Freimer, N.B.; Ferrucci, L.; Erdmann, J.; Elliott, P.; Ejebe, K.G.; Döring, A.; Dominiczak, A.F.; Demissie, S.; Deloukas, P.; de Geus, E.J.; de Faire, U.; Crawford, G.; Collins, F.S.; Chen, Y.D.; Caulfield, M.J.; Campbell, H.; Burtt, N.P.; Bonnycastle, L.L.; Boomsma, D.I.; Boekholdt, S.M.; Bergman, R.N.; Barroso, I.; Bandinelli, S.; Ballantyne, C.M.; Assimes, T.L.; Quertermous, T.; Altshuler, D.; Seielstad, M.; Wong, T.Y.; Tai, E.S.; Feranil, A.B.; Kuzawa, C.W.; Adair, L.S.; Taylor, H.A.; Borecki, I.B.; Gabriel, S.B.; Wilson, J.G.; Holm, H.; Thorsteinsdottir, U.; Gudnason, V.; Krauss, R.M.; Mohlke, K.L.; Ordovas, J.M.; Munroe, P.B.; Kooner, J.S.; Tall, A.R.; Hegele, R.A.; Kastelein, J.J.; Schadt, E.E.; Rotter, J.I.; Boerwinkle, E.; Strachan, D.P.; Mooser, V.; Stefansson, K.; Reilly, M.P.; Samani, N.J.; Schunkert, H.; Cupples, L.A.; Sandhu, M.S.; Ridker, P.M.; Rader, D.J.; van Duijn, C.M.; Peltonen, L.; Abecasis, G.R.; Boehnke, M.; Kathiresan, S.

doi:10.1038/nature09270

Biological, clinical and population relevance of 95 loci for blood lipids.

Détails

Demande d'une copie Sous embargo indéterminé.
Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
Licence: Non spécifiée

ID Serval

serval:BIB_A6D30E0F6FD6

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

Biological, clinical and population relevance of 95 loci for blood lipids.

Périodique

Nature

Auteur⸱e⸱s

Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J., Johansen C.T., Fouchier S.W., Isaacs A., Peloso G.M., Barbalic M., Ricketts S.L., Bis J.C., Aulchenko Y.S., Thorleifsson G., Feitosa M.F., Chambers J., Orho-Melander M., Melander O., Johnson T., Li X., Guo X., Li M., Shin Cho Y., Jin Go M., Jin Kim Y., Lee J.Y., Park T., Kim K., Sim X., Twee-Hee Ong R., Croteau-Chonka D.C., Lange L.A., Smith J.D., Song K., Hua Zhao J., Yuan X., Luan J., Lamina C., Ziegler A., Zhang W., Zee R.Y., Wright A.F., Witteman J.C., Wilson J.F., Willemsen G., Wichmann H.E., Whitfield J.B., Waterworth D.M., Wareham N.J., Waeber G., Vollenweider P., Voight B.F., Vitart V., Uitterlinden A.G., Uda M., Tuomilehto J., Thompson J.R., Tanaka T., Surakka I., Stringham H.M., Spector T.D., Soranzo N., Smit J.H., Sinisalo J., Silander K., Sijbrands E.J., Scuteri A., Scott J., Schlessinger D., Sanna S., Salomaa V., Saharinen J., Sabatti C., Ruokonen A., Rudan I., Rose L.M., Roberts R., Rieder M., Psaty B.M., Pramstaller P.P., Pichler I., Perola M., Penninx B.W., Pedersen N.L., Pattaro C., Parker A.N., Pare G., Oostra B.A., O'Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W., Meitinger T., McPherson R., McCarthy M.I., McArdle W., Masson D., Martin N.G., Marroni F., Mangino M., Magnusson P.K., Lucas G., Luben R., Loos R.J., Lokki M.L., Lettre G., Langenberg C., Launer L.J., Lakatta E.G., Laaksonen R., Kyvik K.O., Kronenberg F., König I.R., Khaw K.T., Kaprio J., Kaplan L.M., Johansson A., Jarvelin M.R., Janssens A.C., Ingelsson E., Igl W., Kees Hovingh G., Hottenga J.J., Hofman A., Hicks A.A., Hengstenberg C., Heid I.M., Hayward C., Havulinna A.S., Hastie N.D., Harris T.B., Haritunians T., Hall A.S., Gyllensten U., Guiducci C., Groop L.C., Gonzalez E., Gieger C., Freimer N.B., Ferrucci L., Erdmann J., Elliott P., Ejebe K.G., Döring A., Dominiczak A.F., Demissie S., Deloukas P., de Geus E.J., de Faire U., Crawford G., Collins F.S., Chen Y.D., Caulfield M.J., Campbell H., Burtt N.P., Bonnycastle L.L., Boomsma D.I., Boekholdt S.M., Bergman R.N., Barroso I., Bandinelli S., Ballantyne C.M., Assimes T.L., Quertermous T., Altshuler D., Seielstad M., Wong T.Y., Tai E.S., Feranil A.B., Kuzawa C.W., Adair L.S., Taylor H.A., Borecki I.B., Gabriel S.B., Wilson J.G., Holm H., Thorsteinsdottir U., Gudnason V., Krauss R.M., Mohlke K.L., Ordovas J.M., Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J., Schadt E.E., Rotter J.I., Boerwinkle E., Strachan D.P., Mooser V., Stefansson K., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A., Sandhu M.S., Ridker P.M., Rader D.J., van Duijn C.M., Peltonen L., Abecasis G.R., Boehnke M., Kathiresan S.

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Statut éditorial

Publié

Date de publication

2010

Peer-reviewed

Oui

Volume

466

Numéro

7307

Pages

707-713

Langue

anglais

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Résumé

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Mots-clé

African Americans/genetics, Animals, Asian Continental Ancestry Group/genetics, Cholesterol, HDL/blood, Cholesterol, LDL/blood, Coronary Artery Disease/blood, Coronary Artery Disease/genetics, Europe/ethnology, European Continental Ancestry Group/genetics, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genotype, Humans, Lipid Metabolism/genetics, Lipids/blood, Liver/metabolism, Male, Mice, N-Acetylgalactosaminyltransferases/genetics, N-Acetylgalactosaminyltransferases/metabolism, Phenotype, Polymorphism, Single Nucleotide/genetics, Protein Phosphatase 1/genetics, Protein Phosphatase 1/metabolism, Reproducibility of Results, Triglycerides/blood

OAI-PMH

oai:serval.unil.ch:BIB_A6D30E0F6FD6

DOI

10.1038/nature09270

Pubmed

20686565

Web of science

000280562500029

Création de la notice

24/08/2010 16:38

Dernière modification de la notice

30/04/2021 6:36

Données d'usage

SERVAL

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Biological, clinical and population relevance of 95 loci for blood lipids.

Détails