Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Autoria(s): Dastani, Z.; Hivert, M.F.; Timpson, N.; Perry, J.R.; Yuan, X.; Scott, R.A.; Henneman, P.; Heid, I.M.; Kizer, J.R.; Lyytikäinen, L.P.; Fuchsberger, C.; Tanaka, T.; Morris, A.P.; Small, K.; Isaacs, A.; Beekman, M.; Coassin, S.; Lohman, K.; Qi, L.; Kanoni, S.; Pankow, J.S.; Uh, H.W.; Wu, Y.; Bidulescu, A.; Rasmussen-Torvik, L.J.; Greenwood, C.M.; Ladouceur, M.; Grimsby, J.; Manning, A.K.; Liu, C.T.; Kooner, J.; Mooser, V.E.; Vollenweider, P.; Kapur, K.A.; Chambers, J.; Wareham, N.J.; Langenberg, C.; Frants, R.; Willems-Vandijk, K.; Oostra, B.A.; Willems, S.M.; Lamina, C.; Winkler, T.W.; Psaty, B.M.; Tracy, R.P.; Brody, J.; Chen, I.; Viikari, J.; Kähönen, M.; Pramstaller, P.P.; Evans, D.M.; St Pourcain, B.; Sattar, N.; Wood, A.R.; Bandinelli, S.; Carlson, O.D.; Egan, J.M.; Böhringer, S.; van Heemst, D.; Kedenko, L.; Kristiansson, K.; Nuotio, M.L.; Loo, B.M.; Harris, T.; Garcia, M.; Kanaya, A.; Haun, M.; Klopp, N.; Wichmann, H.E.; Deloukas, P.; Katsareli, E.; Couper, D.J.; Duncan, B.B.; Kloppenburg, M.; Adair, L.S.; Borja, J.B.; Wilson, J.G.; Wilson, J.G.; Musani, S.; Guo, X.; Johnson, T.; Semple, R.; Teslovich, T.M.; Allison, M.A.; Redline, S.; Buxbaum, S.G.; Mohlke, K.L.; Meulenbelt, I.; Ballantyne, C.M.; Dedoussis, G.V.; Hu, F.B.; Liu, Y.; Paulweber, B.; Spector, T.D.; Slagboom, P.E.; Ferrucci, L.; Jula, A.; Perola, M.; Raitakari, O.; Florez, J.C.; Salomaa, V.; Eriksson, J.G.; Frayling, T.M.; Hicks, A.A.; Lehtimäki, T.; Smith, G.D.; Siscovick, D.S.; Kronenberg, F.; van Duijn, C.; Loos, R.J.; Waterworth, D.M.; Meigs, J.B.; Dupuis, J.; Richards, J.B.; Voight, B.F.; Scott, L.J.; Steinthorsdottir, V.; Dina, C.; Welch, R.P.; Zeggini, E.; Huth, C.; Aulchenko, Y.S.; Thorleifsson, G.; McCulloch, L.J.; Ferreira, T.; Grallert, H.; Amin, N.; Wu, G.; Willer, C.J.; Raychaudhuri, S.; McCarroll, S.A.; Hofmann, O.M.; Segrè, A.V.; van Hoek, M.; Navarro, P.; Ardlie, K.; Balkau, B.; Benediktsson, R.; Bennett, A.J.; Blagieva, R.; Boerwinkle, E.; Bonnycastle, L.L.; Boström, K.B.; Bravenboer, B.; Bumpstead, S.; Burtt, N.P.; Charpentier, G.; Chines, P.S.; Cornelis, M.; Crawford, G.; Doney, A.S.; Elliott, K.S.; Elliott, A.L.; Erdos, M.R.; Fox, C.S.; Franklin, C.S.; Ganser, M.; Gieger, C.; Grarup, N.; Green, T.; Griffin, S.; Groves, C.J.; Guiducci, C.; Hadjadj, S.; Hassanali, N.; Herder, C.; Isomaa, B.; Jackson, A.U.; Johnson, P.R.; Jørgensen, T.; Kao, W.H.; Kong, A.; Kraft, P.; Kuusisto, J.; Lauritzen, T.; Li, M.; Lieverse, A.; Lindgren, C.M.; Lyssenko, V.; Marre, M.; Meitinger, T.; Midthjell, K.; Morken, M.A.; Narisu, N.; Nilsson, P.; Owen, K.R.; Payne, F.; Petersen, A.K.; Platou, C.; Proença, C.; Prokopenko, I.; Rathmann, W.; Rayner, N.W.; Robertson, N.R.; Rocheleau, G.; Roden, M.; Sampson, M.J.; Saxena, R.; Shields, B.M.; Shrader, P.; Sigurdsson, G.; Sparsø, T.; Strassburger, K.; Stringham, H.M.; Sun, Q.; Swift, A.J.; Thorand, B.; Tichet, J.; Tuomi, T.; van Dam, R.M.; van Haeften, T.W.; van Herpt, T.; van Vliet-Ostaptchouk, J.V.; Walters, G.B.; Weedon, M.N.; Wijmenga, C.; Witteman, J.; Bergman, R.N.; Cauchi, S.; Collins, F.S.; Gloyn, A.L.; Gyllensten, U.; Hansen, T.; Hide, W.A.; Hitman, G.A.; Hofman, A.; Hunter, D.J.; Hveem, K.; Laakso, M.; Morris, A.D.; Palmer, C.N.; Rudan, I.; Sijbrands, E.; Stein, L.D.; Tuomilehto, J.; Uitterlinden, A.; Walker, M.; Watanabe, R.M.; Abecasis, G.R.; Boehm, B.O.; Campbell, H.; Daly, M.J.; Hattersley, A.T.; Pedersen, O.; Barroso, I.; Groop, L.; Sladek, R.; Thorsteinsdottir, U.; Wilson, J.F.; Illig, T.; Froguel, P.; van Duijn, C.M.; Stefansson, K.; Altshuler, D.; Boehnke, M.; McCarthy, M.I.; Soranzo, N.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Mägi, R.; Randall, J.; Elliott, P.; Rybin, D.; Dehghan, A.; Hottenga, J.J.; Song, K.; Goel, A.; Lajunen, T.; Doney, A.; Cavalcanti-Proença, C.; Kumari, M.; Timpson, N.J.; Zabena, C.; Ingelsson, E.; An, P.; O'Connell, J.; Luan, J.; Elliott, A.; McCarroll, S.A.; Roccasecca, R.M.; Pattou, F.; Sethupathy, P.; Ariyurek, Y.; Barter, P.; Beilby, J.P.; Ben-Shlomo, Y.; Bergmann, S.; Bochud, M.; Bonnefond, A.; Borch-Johnsen, K.; Böttcher, Y.; Brunner, E.; Bumpstead, S.J.; Chen, Y.D.; Chines, P.; Clarke, R.; Coin, L.J.; Cooper, M.N.; Crisponi, L.; Day, I.N.; de Geus, E.J.; Delplanque, J.; Fedson, A.C.; Fischer-Rosinsky, A.; Forouhi, N.G.; Franzosi, M.G.; Galan, P.; Goodarzi, M.O.; Graessler, J.; Grundy, S.; Gwilliam, R.; Hallmans, G.; Hammond, N.; Han, X.; Hartikainen, A.L.; Hayward, C.; Heath, S.C.; Hercberg, S.; Hillman, D.R.; Hingorani, A.D.; Hui, J.; Hung, J.; Kaakinen, M.; Kaprio, J.; Kesaniemi, Y.A.; Kivimaki, M.; Knight, B.; Koskinen, S.; Kovacs, P.; Kyvik, K.O.; Lathrop, G.M.; Lawlor, D.A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Mahley, R.; Mangino, M.; Martínez-Larrad, M.T.; McAteer, J.B.; McPherson, R.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B.D.; Mukherjee, S.; Naitza, S.; Neville, M.J.; Orrù, M.; Pakyz, R.; Paolisso, G.; Pattaro, C.; Pearson, D.; Peden, J.F.; Pedersen, N.L.; Pfeiffer, A.F.; Pichler, I.; Polasek, O.; Posthuma, D.; Potter, S.C.; Pouta, A.; Province, M.A.; Rayner, N.W.; Rice, K.; Ripatti, S.; Rivadeneira, F.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sanna, S.; Sayer, A.A.; Scheet, P.; Seedorf, U.; Sharp, S.J.; Shields, B.; Sigurðsson, G.; Sijbrands, E.J.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N.L.; Sovio, U.; Swift, A.; Syddall, H.; Syvänen, A.C.; Tönjes, A.; Uitterlinden, A.G.; van Dijk, K.W.; Varma, D.; Visvikis-Siest, S.; Vitart, V.; Vogelzangs, N.; Waeber, G.; Wagner, P.J.; Walley, A.; Ward, K.L.; Watkins, H.; Wild, S.H.; Willemsen, G.; Witteman, J.C.; Yarnell, J.W.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J.H.; Zillikens, M.C.; Borecki, I.B.; Borecki, I.B.; Meneton, P.; Magnusson, P.K.; Nathan, D.M.; Williams, G.H.; Silander, K.; Bornstein, S.R.; Schwarz, P.; Spranger, J.; Karpe, F.; Shuldiner, A.R.; Cooper, C.; Serrano-Ríos, M.; Lind, L.; Palmer, L.J.; Hu, F.B.; Franks, P.W.; Ebrahim, S.; Marmot, M.; Kao, W.H.; Pramstaller, P.P.; Wright, A.F.; Stumvoll, M.; Hamsten, A.; Buchanan, T.A.; Buchanan, T.A.; Valle, T.T.; Rotter, J.I.; Penninx, B.W.; Boomsma, D.I.; Cao, A.; Scuteri, A.; Schlessinger, D.; Uda, M.; Ruokonen, A.; Jarvelin, M.R.; Peltonen, L.; Mooser, V.; Sladek, R.; Musunuru, K.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Chasman, D.I.; Johansen, C.T.; Fouchier, S.W.; Peloso, G.M.; Barbalic, M.; Ricketts, S.L.; Bis, J.C.; Feitosa, M.F.; Orho-Melander, M.; Melander, O.; Li, X.; Li, M.; Cho, Y.S.; Go, M.J.; Kim, Y.J.; Lee, J.Y.; Park, T.; Kim, K.; Sim, X.; Ong, R.T.; Croteau-Chonka, D.C.; Lange, L.A.; Smith, J.D.; Ziegler, A.; Zhang, W.; Zee, R.Y.; Whitfield, J.B.; Thompson, J.R.; Surakka, I.; Spector, T.D.; Smit, J.H.; Sinisalo, J.; Scott, J.; Saharinen, J.; Sabatti, C.; Rose, L.M.; Roberts, R.; Rieder, M.; Parker, A.N.; Pare, G.; O'Donnell, C.J.; Nieminen, M.S.; Nickerson, D.A.; Montgomery, G.W.; McArdle, W.; Masson, D.; Martin, N.G.; Marroni, F.; Lucas, G.; Luben, R.; Lokki, M.L.; Lettre, G.; Launer, L.J.; Lakatta, E.G.; Laaksonen, R.; Kyvik, K.O.; König, I.R.; Khaw, K.T.; Kaplan, L.M.; Johansson, Å.; Janssens, A.C.; Igl, W.; Hovingh, G.K.; Hengstenberg, C.; Havulinna, A.S.; Hastie, N.D.; Harris, T.B.; Haritunians, T.; Hall, A.S.; Groop, L.C.; Gonzalez, E.; Freimer, N.B.; Erdmann, J.; Ejebe, K.G.; Döring, A.; Dominiczak, A.F.; Demissie, S.; Deloukas, P.; de Faire, U.; Crawford, G.; Chen, Y.D.; Caulfield, M.J.; Boekholdt, S.M.; Assimes, T.L.; Quertermous, T.; Seielstad, M.; Wong, T.Y.; Tai, E.S.; Feranil, A.B.; Kuzawa, C.W.; Taylor, H.A.; Gabriel, S.B.; Holm, H.; Gudnason, V.; Krauss, R.M.; Ordovas, J.M.; Munroe, P.B.; Kooner, J.S.; Tall, A.R.; Hegele, R.A.; Kastelein, J.J.; Schadt, E.E.; Strachan, D.P.; Reilly, M.P.; Samani, N.J.; Schunkert, H.; Cupples, L.A.; Sandhu, M.S.; Ridker, P.M.; Rader, D.J.; Kathiresan, S.; Schadt E.E.; Strachan D.P.; Reilly M.P.; Samani N.J.; Schunkert H.; Cupples L.A.; Sandhu M.S.; Ridker P.M.; Rader D.J.; Kathiresan S.
Data(s)

2012
Resumo

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
Identificador

https://serval.unil.ch/notice/serval:BIB_22F2CC6BB4EC

info:pmid:22479202

https://serval.unil.ch/resource/serval:BIB_22F2CC6BB4EC.P001/REF

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_22F2CC6BB4EC4

urn:nbn:ch:serval-BIB_22F2CC6BB4EC4

http://my.unil.ch/serval/document/BIB_22F2CC6BB4EC.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_22F2CC6BB4EC4
Idioma(s)

eng
Direitos

info:eu-repo/semantics/openAccess

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Fonte

Plos Genetics83e1002607
Palavras-Chave #Adiponectin/blood; Adiponectin/genetics; African Americans; Asian Continental Ancestry Group; Cholesterol, HDL/genetics; Diabetes Mellitus, Type 2/genetics; European Continental Ancestry Group; Female; Gene Expression; Genetic Predisposition to Disease; Genome-Wide Association Study; Glucose Tolerance Test; Humans; Insulin Resistance/genetics; Male; Metabolic Networks and Pathways; Polymorphism, Single Nucleotide; Waist-Hip Ratio
Tipo

info:eu-repo/semantics/article

article
Contribuinte(s)

DIAGRAM+ Consortium

MAGIC Consortium

GLGC Investigators

MuTHER Consortium

DIAGRAM Consortium

GIANT Consortium

Global B Pgen Consortium

Procardis Consortium

MAGIC investigators

GLGC Consortium

Olson, J.

Kronmal, R.

Robbins, J.

Chaves, PH.

Burke, G.

Kuller, LH.

Tracy, R.

Gottdiener, J.

Prineas, R.

Becker, JT.

Enright, P.

Klein, R.

O'Leary, DH.
Formato

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