Impact of Common Variation in Bone-Related Genes on Type 2 Diabetes and Related Traits

View/ Open
Author
Billings, Liana K.
Hsu, Yi-Hsiang
Ackerman, Rachel J.
Dupuis, Josée
Voight, Benjamin F.
Rasmussen-Torvik, Laura J.
Hercberg, Serge
Lathrop, Mark
Barnes, Daniel
Langenberg, Claudia
Hui, Jennie
Fu, Mao
Bouatia-Naji, Nabila
Lecoeur, Cecile
An, Ping
Magnusson, Patrik K.
Surakka, Ida
Ripatti, Samuli
Christiansen, Lene
Dalgård, Christine
Folkersen, Lasse
Grundberg, Elin
Eriksson, Per
Kaprio, Jaakko
Ohm Kyvik, Kirsten
Pedersen, Nancy L.
Borecki, Ingrid B.
Province, Michael A.
Balkau, Beverley
Froguel, Philippe
Shuldiner, Alan R.
Palmer, Lyle J.
Wareham, Nick
Meneton, Pierre
Johnson, Toby
Pankow, James S.
Karasik, David
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.2337/db11-1515Metadata
Show full item recordCitation
Billings, L. K., Y. Hsu, R. J. Ackerman, J. Dupuis, B. F. Voight, L. J. Rasmussen-Torvik, S. Hercberg, et al. 2012. “Impact of Common Variation in Bone-Related Genes on Type 2 Diabetes and Related Traits.” Diabetes 61 (8): 2176-2186. doi:10.2337/db11-1515. http://dx.doi.org/10.2337/db11-1515.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402303/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855790
Collections
- HMS Scholarly Articles [17875]
Contact administrator regarding this item (to report mistakes or request changes)