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

Manning, Alisa K and Hivert, Marie-France and Scott, Robert A and Grimsby, Jonna L and Bouatia-Naji, Nabila and Chen, Han and Rybin, Denis and Liu, Ching-Ti and Bielak, Lawrence F and Prokopenko, Inga and Amin, Najaf and Barnes, Daniel and Cadby, Gemma and Hottenga, Jouke-Jan and Ingelsson, Erik and Jackson, Anne U and Johnson, Toby and Kanoni, Stavroula and Ladenvall, Claes and Lagou, Vasiliki and Lahti, Jari and Lecoeur, Cecile and Liu, Yongmei and Martinez-Larrad, Maria Teresa and Montasser, May E and Navarro, Pau and Perry, John R B and Rasmussen-Torvik, Laura J and Salo, Perttu and Sattar, Naveed and Shungin, Dmitry and Strawbridge, Rona J and Tanaka, Toshiko and van Duijn, Cornelia M and An, Ping and de Andrade, Mariza and Andrews, Jeanette S and Aspelund, Thor and Atalay, Mustafa and Aulchenko, Yurii and Balkau, Beverley and Bandinelli, Stefania and Beckmann, Jacques S and Beilby, John P and Bellis, Claire and Bergman, Richard N and Blangero, John and Boban, Mladen and Boehnke, Michael and Boerwinkle, Eric and Bonnycastle, Lori L and Boomsma, Dorret I and Borecki, Ingrid B and Böttcher, Yvonne and Bouchard, Claude and Brunner, Eric and Budimir, Danijela and Campbell, Harry and Carlson, Olga and Chines, Peter S and Clarke, Robert and Collins, Francis S and Corbatón-Anchuelo, Arturo and Couper, David and de Faire, Ulf and Dedoussis, George V and Deloukas, Panos and Dimitriou, Maria and Egan, Josephine M and Eiriksdottir, Gudny and Erdos, Michael R and Eriksson, Johan G and Eury, Elodie and Ferrucci, Luigi and Ford, Ian and Forouhi, Nita G and Fox, Caroline S and Franzosi, Maria Grazia and Franks, Paul W and Frayling, Timothy M and Froguel, Philippe and Galan, Pilar and de Geus, Eco and Gigante, Bruna and Glazer, Nicole L and Goel, Anuj and Groop, Leif and Gudnason, Vilmundur and Hallmans, Göran and Hamsten, Anders and Hansson, Ola and Harris, Tamara B and Hayward, Caroline and Heath, Simon and Hercberg, Serge and Hicks, Andrew A and Hingorani, Aroon and Hofman, Albert and Hui, Jennie and Hung, Joseph and Jarvelin, Marjo-Riitta and Jhun, Min A and Johnson, Paul C D and Jukema, J Wouter and Jula, Antti and Kao, W H and Kaprio, Jaakko and Kardia, Sharon L R and Keinanen-Kiukaanniemi, Sirkka and Kivimaki, Mika and Kolcic, Ivana and Kovacs, Peter and Kumari, Meena and Kuusisto, Johanna and Kyvik, Kirsten Ohm and Laakso, Markku and Lakka, Timo and Lannfelt, Lars and Lathrop, G Mark and Launer, Lenore J and Leander, Karin and Li, Guo and Lind, Lars and Lindstrom, Jaana and Lobbens, Stéphane and Loos, Ruth J F and Luan, Jian'an and Lyssenko, Valeriya and Mägi, Reedik and Magnusson, Patrik K E and Marmot, Michael and Meneton, Pierre and Mohlke, Karen L and Mooser, Vincent and Morken, Mario A and Miljkovic, Iva and Narisu, Narisu and O'Connell, Jeff and Ong, Ken K and Oostra, Ben A and Palmer, Lyle J and Palotie, Aarno and Pankow, James S and Peden, John F and Pedersen, Nancy L and Pehlic, Marina and Peltonen, Leena and Penninx, Brenda and Pericic, Marijana and Perola, Markus and Perusse, Louis and Peyser, Patricia A and Polasek, Ozren and Pramstaller, Peter P and Province, Michael A and Räikkönen, Katri and Rauramaa, Rainer and Rehnberg, Emil and Rice, Ken and Rotter, Jerome I and Rudan, Igor and Ruokonen, Aimo and Saaristo, Timo and Sabater-Lleal, Maria and Salomaa, Veikko and Savage, David B and Saxena, Richa and Schwarz, Peter and Seedorf, Udo and Sennblad, Bengt and Serrano-Rios, Manuel and Shuldiner, Alan R and Sijbrands, Eric J G and Siscovick, David S and Smit, Johannes H and Small, Kerrin S and Smith, Nicholas L and Smith, Albert Vernon and Stančáková, Alena and Stirrups, Kathleen and Stumvoll, Michael and Sun, Yan V and Swift, Amy J and Tönjes, Anke and Tuomilehto, Jaakko and Trompet, Stella and Uitterlinden, Andre G and Uusitupa, Matti and Vikström, Max and Vitart, Veronique and Vohl, Marie-Claude and Voight, Benjamin F and Vollenweider, Peter and Waeber, Gerard and Waterworth, Dawn M and Watkins, Hugh and Wheeler, Eleanor and Widen, Elisabeth and Wild, Sarah H and Willems, Sara M and Willemsen, Gonneke and Wilson, James F and Witteman, Jacqueline C M and Wright, Alan F and Yaghootkar, Hanieh and Zelenika, Diana and Zemunik, Tatijana and Zgaga, Lina and Wareham, Nicholas J and McCarthy, Mark I and Barroso, Ines and Watanabe, Richard M and Florez, Jose C and Dupuis, Josée and Meigs, James B and Langenberg, Claudia and Tsaprouni, Loukia (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nature genetics, 44 (6). pp. 659-669. ISSN 1546-1718

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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.

Item Type: Article
Subjects: C100 Biology
C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
Divisions: UoA Collections > REF2021 UoA 03: Allied Health Professions, Dentistry, Nursing & Pharmacy
Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Loukia Tsaprouni
Date Deposited: 17 Jul 2017 08:44
Last Modified: 17 Jul 2017 08:44
URI: http://www.open-access.bcu.ac.uk/id/eprint/4789

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