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Impact of common variation in bone-related genes on type 2 diabetes and related traits

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dc.contributor.authorBillings, L.
dc.contributor.authorHsu, Y.
dc.contributor.authorAckerman, R.
dc.contributor.authorDupuis, J.
dc.contributor.authorVoight, B.
dc.contributor.authorRasmussen-Torvik, L.
dc.contributor.authorHercberg, S.
dc.contributor.authorLathrop, M.
dc.contributor.authorBarnes, D.
dc.contributor.authorLangenberg, C.
dc.contributor.authorHui, J.
dc.contributor.authorFu, M.
dc.contributor.authorBouatia-Naji, N.
dc.contributor.authorLecoeur, C.
dc.contributor.authorAn, P.
dc.contributor.authorMagnusson, P.
dc.contributor.authorSurakka, I.
dc.contributor.authorRipatti, S.
dc.contributor.authorChristiansen, L.
dc.contributor.authorDalgard, C.
dc.contributor.authoret al.
dc.date.issued2012
dc.description.abstractExploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r2 > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post–oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations.
dc.description.statementofresponsibilityLiana K. Billings, Yi-Hsiang Hsu, Rachel J. Ackerman, Josée Dupuis, Benjamin F. Voight, Laura J. Rasmussen-Torvik, Serge Hercberg, Mark Lathrop, Daniel Barnes, Claudia Langenberg, Jennie Hui, Mao Fu, Nabila Bouatia-Naji, Cecile Lecoeur, Ping An, Patrik K. Magnusson, Ida Surakka, Samuli Ripatti, Lene Christiansen, Christine Dalgård, Lasse Folkersen, Elin Grundberg, the MAGIC Investigators, the DIAGRAM, Consortium, the MuTHER Consortium, the ASCOT Investigators, the GEFOS Consortium, Per Eriksson, Jaakko Kaprio, Kirsten Ohm Kyvik, Nancy L. Pedersen, Ingrid B. Borecki, Michael A. Province, Beverley Balkau, Philippe Froguel, Alan R. Shuldiner, Lyle J. Palmer, Nick Wareham, Pierre Meneton, Toby Johnson, James S. Pankow, David Karasik, James B. Meigs, Douglas P. Kiel, and Jose C. Florez
dc.identifier.citationDiabetes, 2012; 61(8):2176-2186
dc.identifier.doi10.2337/db11-1515
dc.identifier.issn0012-1797
dc.identifier.issn1939-327X
dc.identifier.urihttp://hdl.handle.net/2440/88223
dc.language.isoen
dc.publisherAmerican Diabetes Association
dc.relation.grantHEALTH-F4-2007-201413
dc.rights© 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details
dc.source.urihttps://doi.org/10.2337/db11-1515
dc.subjectMAGIC Investigators
dc.subjectDIAGRAM + Consortium
dc.subjectMuTHER Consortium
dc.subjectASCOT Investigators
dc.subjectGEFOS Consortium
dc.subjectLiver
dc.subjectAdipose Tissue
dc.subjectHumans
dc.subjectOsteoporosis
dc.subjectDiabetes Mellitus, Type 2
dc.subjectMicrofilament Proteins
dc.subjectInsulin
dc.subjectBlood Glucose
dc.subjectIntegrin alpha1
dc.subjectBody Mass Index
dc.subjectBone Density
dc.subjectLinkage Disequilibrium
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectFemale
dc.subjectFractures, Bone
dc.subjectGenome-Wide Association Study
dc.titleImpact of common variation in bone-related genes on type 2 diabetes and related traits
dc.typeJournal article
pubs.publication-statusPublished

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