A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Autoria(s): Manning, A.K.; Hivert, M.F.; Scott, R.A.; Grimsby, J.L.; Bouatia-Naji, N.; Chen, H.; Rybin, D.; Liu, C.T.; Bielak, L.F.; Prokopenko, I.; Amin, N.; Barnes, D.; Cadby, G.; Hottenga, J.J.; Ingelsson, E.; Jackson, A.U.; Johnson, T.; Kanoni, S.; Ladenvall, C.; Lagou, V.; Lahti, J.; Lecoeur, C.; Liu, Y.; Martinez-Larrad, M.T.; Montasser, M.E.; Navarro, P.; Perry, J.R.; Rasmussen-Torvik, L.J.; Salo, P.; Sattar, N.; Shungin, D.; Strawbridge, R.J.; Tanaka, T.; van Duijn, C.M.; An, P.; de Andrade, M.; Andrews, J.S.; Aspelund, T.; Atalay, M.; Aulchenko, Y.; Balkau, B.; Bandinelli, S.; Beckmann, J.S.; Beilby, J.P.; Bellis, C.; Bergman, R.N.; Blangero, J.; Boban, M.; Boehnke, M.; Boerwinkle, E.; Bonnycastle, L.L.; Boomsma, D.I.; Borecki, I.B.; Böttcher, Y.; Bouchard, C.; Brunner, E.; Budimir, D.; Campbell, H.; Carlson, O.; Chines, P.S.; Clarke, R.; Collins, F.S.; Corbatón-Anchuelo, A.; Couper, D.; de Faire, U.; Dedoussis, G.V.; Deloukas, P.; Dimitriou, M.; Egan, J.M.; Eiriksdottir, G.; Erdos, M.R.; Eriksson, J.G.; Eury, E.; Ferrucci, L.; Ford, I.; Forouhi, N.G.; Fox, C.S.; Franzosi, M.G.; Franks, P.W.; Frayling, T.M.; Froguel, P.; Galan, P.; de Geus, E.; Gigante, B.; Glazer, N.L.; Goel, A.; Groop, L.; Gudnason, V.; Hallmans, G.; Hamsten, A.; Hansson, O.; Harris, T.B.; Hayward, C.; Heath, S.; Hercberg, S.; Hicks, A.A.; Hingorani, A.; Hofman, A.; Hui, J.; Hung, J.; Jarvelin, M.R.; Jhun, M.A.; Johnson, P.C.; Jukema, J.W.; Jula, A.; Kao, W.H.; Kaprio, J.; Kardia, S.L.; Keinanen-Kiukaanniemi, S.; Kivimaki, M.; Kolcic, I.; Kovacs, P.; Kumari, M.; Kuusisto, J.; Kyvik, K.O.; Laakso, M.; Lakka, T.; Lannfelt, L.; Lathrop, G.M.; Launer, L.J.; Leander, K.; Li, G.; Lind, L.; Lindstrom, J.; Lobbens, S.; Loos, R.J.; Luan, J.; Lyssenko, V.; Mägi, R.; Magnusson, P.K.; Marmot, M.; Meneton, P.; Mohlke, K.L.; Mooser, V.; Morken, M.A.; Miljkovic, I.; Narisu, N.; O'Connell, J.; Ong, K.K.; Oostra, B.A.; Palmer, L.J.; Palotie, A.; Pankow, J.S.; Peden, J.F.; Pedersen, N.L.; Pehlic, M.; Peltonen, L.; Penninx, B.; Pericic, M.; Perola, M.; Perusse, L.; Peyser, P.A.; Polasek, O.; Pramstaller, P.P.; Province, M.A.; Räikkönen, K.; Rauramaa, R.; Rehnberg, E.; Rice, K.; Rotter, J.I.; Rudan, I.; Ruokonen, A.; Saaristo, T.; Sabater-Lleal, M.; Salomaa, V.; Savage, D.B.; Saxena, R.; Schwarz, P.; Seedorf, U.; Sennblad, B.; Serrano-Rios, M.; Shuldiner, A.R.; Sijbrands, E.J.; Siscovick, D.S.; Smit, J.H.; Small, K.S.; Smith, N.L.; Smith, A.V.; Stančáková, A.; Stirrups, K.; Stumvoll, M.; Sun, Y.V.; Swift, A.J.; Tönjes, A.; Tuomilehto, J.; Trompet, S.; Uitterlinden, A.G.; Uusitupa, M.; Vikström, M.; Vitart, V.; Vohl, M.C.; Voight, B.F.; Vollenweider, P.; Waeber, G.; Waterworth, D.M.; Watkins, H.; Wheeler, E.; Widen, E.; Wild, S.H.; Willems, S.M.; Willemsen, G.; Wilson, J.F.; Witteman, J.C.; Wright, A.F.; Yaghootkar, H.; Zelenika, D.; Zemunik, T.; Zgaga, L.; Wareham, N.J.; McCarthy, M.I.; Barroso, I.; Watanabe, R.M.; Florez, J.C.; Dupuis, J.; Meigs, J.B.; Langenberg, C.; Dupuis J.; Meigs J.B.; Langenberg C.
Data(s)

13/05/2012
Resumo

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
Identificador

https://serval.unil.ch/notice/serval:BIB_73F3460C24D9

info:pmid:22581228

https://serval.unil.ch/resource/serval:BIB_73F3460C24D9.P001/REF

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_73F3460C24D94

urn:nbn:ch:serval-BIB_73F3460C24D94
Idioma(s)

eng
Fonte

Nature genetics446659-669
Palavras-Chave #Blood Glucose/metabolism; Body Mass Index; Cholesterol, HDL/metabolism; Diabetes Mellitus, Type 2/genetics; Genome-Wide Association Study; Humans; Insulin/metabolism; Insulin Resistance/genetics; Polymorphism, Single Nucleotide
Tipo

info:eu-repo/semantics/article

article
Contribuinte(s)

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium

Multiple Tissue Human Expression Resource (MUTHER) Consortium

Ahmadi, K.R.

Ainali, C.

Barrett, A.

Bataille, V.

Bell, J.T.

Buil, A.

Deloukas, P.

Dermitzakis, E.T.

Dimas, A.S.

Durbin, R.

Glass, D.

Grundberg, E.

Hassanali, N.

Hedman, Å.K.

Ingle, C.

Knowles, D.

Krestyaninova, M.

Lindgren, C.M.

Lowe, C.E.

McCarthy, M.I.

Meduri, E.

di Meglio, P.

Min, J.L.

Montgomery, S.B.

Nestle, F.O.

Nica, A.C.

Nisbet, J.

O'Rahilly, S.

Parts, L.

Potter, S.

Sekowska, M.

Shin, S.Y.

Small, K.S.

Soranzo, N.

Spector, T.D.

Surdulescu, G.

Travers, M.E.

Tsaprouni, L.

Tsoka, S.

Wilk, A.

Yang, T.P.

Zondervan, K.T.

Voight, B.F.

Scott, L.J.

Steinthorsdottir, V.

Morris, A.P.

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.

Langenberg, C.

Hofmann, O.M.

Dupuis, J.

Qi, L.

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.

Couper, D.J.

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.

Klopp, N.

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.

Perry, J.R.

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.

Mohlke, K.L.

Morris, A.D.

Palmer, C.N.

Pramstaller, P.P.

Rudan, I.

Sijbrands, E.

Stein, L.D.

Tuomilehto, J.

Uitterlinden, A.

Walker, M.

Wareham, N.J.

Watanabe, R.M.

Abecasis, G.R.

Boehm, B.O.

Campbell, H.

Daly, M.J.

Hattersley, A.T.

Hu, F.B.

Meigs, J.B.

Pankow, J.S.

Pedersen, O.

Wichmann, H.E.

Barroso, I.

Florez, J.C.

Frayling, T.M.

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.
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