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

Title: A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
Authors: Manning, AK; Hivert, MF; Scott, RA; Grimsby, JL; Bouatia-Naji, N; Chen, H; Rybin, D; Liu, CT; Bielak, LF; Prokopenko, I; Amin, Najaf; Barnes, D; Cadby, G; Hottenga, JJ (Jouke Jan); Ingelsson, E; Jackson, AU; Johnson, T; Kanoni, S; Ladenvall, C; Lagou, V; Lahti, J; Lecoeur, C; Liu, YM; Martinez-Larrad, MT; Montasser, ME; Navarro, P; Perry, JRB; Rasmussen-Torvik, LJ; Salo, P; Sattar, N; Shungin, D; Strawbridge, RJ; Tanaka, T; Duijn, Cornelia; An, P; de Andrade, M; Andrews, JS; Aspelund, T; Atalay, M; Aulchenko, Yuriy; Balkau, B; Bandinelli, S; Beckmann, JS; Beilby, JP; Bellis, C; Bergman, RN; Blangero, J; Boban, M; Boehnke, M; Boerwinkle, E; Bonnycastle, LL; Boomsma, DI; Borecki, IB; Boettcher, Y; Bouchard, C; Brunner, E; Budimir, D; Campbell, H; Carlson, O; Chines, PS; Clarke, R; Collins, FS; Corbaton-Anchuelo, A; Couper, D; de Faire, U; Dedoussis, GV; Deloukas, P; Dimitriou, M; Egan, JM; Eiriksdottir, G; Erdos, MR; Eriksson, JG; Eury, E; Ferrucci, L; Ford, I; Forouhi, NG; Fox, CS; Franzosi, MG; Franks, PW; Frayling, TM; Froguel, P; Galan, P; de Geus, ED; Gigante, B; Glazer, NL; Goel, A; Groop, L; Gudnason, V; Hallmans, G; Hamsten, A; Hansson, O; Harris, TB; Hayward, C; Heath, S; Hercberg, S; Hicks, AA; Hingorani, A; Hofman, Bert; Hui, J; Hung, J; Jarvelin, MR; Jhun, MA; Johnson, PCD; Jukema, JW; Jula, A; Kao, WH; Kaprio, J; Kardia, SLR; Keinanen-Kiukaanniemi, S; Kivimaki, M; Kolcic, I; Kovacs, P; Kumari, M; Kuusisto, J; Kyvik, KO; Laakso, M; Lakka, T; Lannfelt, L; Lathrop, GM; Launer, LJ (Lenore); Leander, K; Li, G (Guo); Lind, L; Lindstrom, J; Lobbens, S; Loos, RJF; Luan, JA; Lyssenko, V; Magi, R; Magnusson, PKE; Marmot, M; Meneton, P; Mohlke, KL; Mooser, V; Morken, MA; Miljkovic, I; Narisu, N; O'Connell, J; Ong, KK; Oostra, Ben; Palmer, LJ; Palotie, A; Pankow, JS; Peden, JF; Pedersen, NL; Pehlic, M; Peltonen, L; Penninx, B; Pericic, M; Perola, M; Perusse, L; Peyser, PA; Polasek, O; Pramstaller, PP; Province, MA; Raikkonen, K; Rauramaa, R; Rehnberg, E; Rice, K; Rotter, JI; Rudan, I; Ruokonen, A; Saaristo, T; Sabater-Lleal, M; Salomaa, V; Savage, DB; Saxena, R; Schwarz, P; Seedorf, U; Sennblad, B; Serrano-Rios, M; Shuldiner, AR; Sijbrands, E.J.G.; Siscovick, DS; Smit, JH; Small, KS; Smith, NL; Smith, AV; Stancakova, A; Stirrups, K; Stumvoll, M; Sun, YV; Swift, AJ; Toenjes, A; Tuomilehto, J; Trompet, S; Uitterlinden, André; Uusitupa, M; Vikstrom, M; Vitart, V; Vohl, MC; Voight, BF; Vollenweider, P; Waeber, G; Waterworth, DM; Watkins, H; Wheeler, E; Widen, E; Wild, SH; Willems, SM; Willemsen, G; Wilson, JF; Witteman, JCM; Wright, AF; Yaghootkar, H; Zelenika, D; Zemunik, T; Zgaga, L; Wareham, NJ; McCarthy, MI; Barroso, I; Watanabe, RM; Florez, JC; Dupuis, J; Meigs, JB; Langenberg, C
Source: Manning, AK, Hivert, MF, Scott, RA, Grimsby, JL, Bouatia-Naji, N, Chen, H, Rybin, D, Liu, CT, Bielak, LF, Prokopenko, I, Amin, N, Barnes, D, Cadby, G, Hottenga, JJ, Ingelsson, E, Jackson, AU, Johnson, T, Kanoni, S, Ladenvall, C, Lagou, V, Lahti, J, Lecoeur, C, Liu, YM, Martinez-Larrad, MT, Montasser, ME, Navarro, P, Perry, JRB, Rasmussen-Torvik, LJ, Salo, P, Sattar, N, Shungin, D, Strawbridge, RJ, Tanaka, T, Duijn, C, An, P, de Andrade, M, Andrews, JS, Aspelund, T, Atalay, M, Aulchenko, Y, Balkau, B, Bandinelli, S, Beckmann, JS, Beilby, JP, Bellis, C, Bergman, RN, Blangero, J, Boban, M, Boehnke, M, ....
Publication Year: 2012
Subject Terms: /dk/atira/pure/keywords/researchprograms/AFL001000/EMCCOEUR09; name=EMC COEUR-09; /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMGC029601; name=EMC MGC-02-96-01; /dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM013909A; name=EMC MM-01-39-09-A; /dk/atira/pure/keywords/researchprograms/AFL001000/EMCNIHES016401; name=EMC NIHES-01-64-01; /dk/atira/pure/keywords/researchprograms/AFL001000/EMCNIHES016402; name=EMC NIHES-01-64-02; /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being
Description: Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-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 x 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
ISSN: 1061-4036; 1546-1718
Relation: info:eu-repo/semantics/altIdentifier/pmid/22581228; info:eu-repo/semantics/altIdentifier/pissn/1061-4036; info:eu-repo/semantics/altIdentifier/eissn/1546-1718
DOI: 10.1038/ng.2274
Availability: https://pure.eur.nl/en/publications/2d4f5e0e-d196-41d3-9494-0a32f8dbe938; https://doi.org/10.1038/ng.2274; https://pure.eur.nl/ws/files/47439609/metis_180786_VOR.pdf; https://hdl.handle.net/1765/37912
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.7CD357D6
Database: BASE