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Billings, L.K.* ; Hsu, Y.H.* ; Ackerman, R.J.* ; Dupuis, J.* ; Voight, B.F.* ; Rasmussen-Torvik, L.J.* ; Hercberg, S.* ; Lathrop, M* ; Barnes, D.* ; Langenberg, C.* ; Hui, J.* ; Fu, M.* ; Bouatia-Naji, N.* ; Lecoeur, C.* ; An, P.* ; Magnusson, P.K.* ; Surakka, I.* ; Ripatti, S.* ; Christiansen, L.* ; Dalgård, C.* ; Folkersen, L.* ; Grundberg, E.* ; MAGIC Investigators (Gieger, C. ; Grallert, H. ; Meisinger, C. ; Wichmann, H.-E. ; Thorand, B. ; Illig, T.) ; DIAGRAM Consortium (Huth, C. ; Klopp, N. ; Meitinger, T. ; Thorand, B. ; Grallert, H. ; Gieger, C. ; Wichmann, H.-E. ; Illig, T. ; Petersen, A.-K.) ; MuTHER Consortium (*) ; ASCOT Investigators (*) ; GEFOS Consortium (*) ; Eriksson, P.* ; Kaprio, J.* ; Ohm Kyvik, K.* ; Pedersen, N.L.* ; Borecki, I.B.* ; Province, M.A.* ; Balkau, B.* ; Froguel, P.* ; Shuldiner, A.R.* ; Palmer, L.J.* ; Wareham, N.J.* ; Meneton, P.* ; Johnson, T.* ; Pankow, J.S.* ; Karasik, D.* ; Meigs, J.B.* ; Kiel, D.P.* ; Florez, J.C*

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

Diabetes 61, 2176-2186 (2012)
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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 (r(2) > 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; MINERAL DENSITY; FRACTURE RISK; OSTEOPOROTIC FRACTURES; INSULIN-RESISTANCE; ENERGY-METABOLISM; FASTING GLUCOSE; LOCI; METAANALYSIS
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 61, Issue: 8, Pages: 2176-2186 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504200-002
G-504100-001
G-504000-002
G-503900-002
PubMed ID 22698912
DOI 10.2337/db11-1515
WOS ID 000306891100033
Erfassungsdatum 2012-08-31
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