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Type: Journal article
Title: Impact of common variation in bone-related genes on type 2 diabetes and related traits
Author: Billings, L.
Hsu, Y.
Ackerman, R.
Dupuis, J.
Voight, B.
Rasmussen-Torvik, L.
Hercberg, S.
Lathrop, M.
Barnes, D.
Langenberg, C.
Hui, J.
Fu, M.
Bouatia-Naji, N.
Lecoeur, C.
An, P.
Magnusson, P.
Surakka, I.
Ripatti, S.
Christiansen, L.
Dalgard, C.
et al.
Citation: Diabetes, 2012; 61(8):2176-2186
Publisher: American Diabetes Association
Issue Date: 2012
ISSN: 0012-1797
Statement of
Liana 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
Abstract: Exploring 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.
Keywords: MAGIC Investigators; DIAGRAM + Consortium; MuTHER Consortium; ASCOT Investigators; GEFOS Consortium; Liver; Adipose Tissue; Humans; Osteoporosis; Diabetes Mellitus, Type 2; Microfilament Proteins; Insulin; Blood Glucose; Integrin alpha1; Body Mass Index; Bone Density; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Adult; Female; Fractures, Bone; Genome-Wide Association Study
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 for details
RMID: 0020136608
DOI: 10.2337/db11-1515
Appears in Collections:Translational Health Science publications

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