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

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dc.contributor.authorPalmer, L.
dc.contributor.authorManning, A.K.
dc.contributor.authorHivert M-, F.
dc.contributor.authorScott, R.A.
dc.contributor.authorGrimsby, J.L.
dc.contributor.authorBouatia-Naji, N.
dc.contributor.authorChen, H.
dc.contributor.authorRybin, D.
dc.contributor.authorLiu C-, T.
dc.contributor.authorBielak, L.F.
dc.contributor.authorProkopenko, I.
dc.contributor.authorAmin, N.
dc.contributor.authorBarnes, D.
dc.contributor.authorCadby, G.
dc.contributor.authorHottenga J-, J.
dc.contributor.authorIngelsson, E.
dc.contributor.authorJackson, A.U.
dc.contributor.authorJohnson, T.
dc.contributor.authorKanoni, S.
dc.contributor.authorLadenvall, C.
dc.contributor.authoret al.
dc.date.issued2012
dc.description.abstractRecent 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.
dc.description.statementofresponsibilityAlisa K Manning ... Lyle J Palmer ... DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, The Multiple Tissue Human Expression Resource (MUTHER) Consortium ... et al.
dc.identifier.citationNature Genetics, 2012; 44(6):659-669
dc.identifier.doi10.1038/ng.2274
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.orcidPalmer, L. [0000-0002-1628-3055]
dc.identifier.urihttp://hdl.handle.net/2440/88620
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2012 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/ng.2274
dc.subjectDIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
dc.subjectMultiple Tissue Human Expression Resource (MUTHER) Consortium
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectInsulin Resistance
dc.subjectInsulin
dc.subjectBlood Glucose
dc.subjectBody Mass Index
dc.subjectCholesterol, HDL
dc.subjectGenome-Wide Association Study
dc.subjectPolymorphism, Single Nucleotide
dc.titleA genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
dc.typeJournal article
pubs.publication-statusPublished

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