A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
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State: Public
Version: author
State: Public
Version: author
Serval ID
serval:BIB_73F3460C24D9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
Journal
Nature genetics
Working group(s)
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium
Contributor(s)
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.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
13/05/2012
Peer-reviewed
Oui
Volume
44
Number
6
Pages
659-669
Language
english
Notes
Publication types: Journal Article ; Meta-Analysis
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
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
Pubmed
Create date
06/06/2012 15:59
Last modification date
20/08/2019 15:31