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

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; 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; Jose C. Florez

doi:https://doi.org/10.2337/db11-1515

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

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 DalgårdLasse Folkersen, Elin Grundberg, 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, Jose C. Florez

Research output: Contribution to journal › Article › peer-review

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 (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.

Original language	English
Pages (from-to)	2176-2186
Number of pages	11
Journal	Diabetes
Volume	61
Issue number	8
DOIs	https://doi.org/10.2337/db11-1515
State	Published - Aug 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

https://doi.org/10.2337/db11-1515

Cite this

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., ... Florez, J. C. (2012). Impact of common variation in bone-related genes on type 2 diabetes and related traits. Diabetes, 61(8), 2176-2186. https://doi.org/10.2337/db11-1515

@article{4a3ffeae52c448f980f6ed8dc25c365b,

title = "Impact of common variation in bone-related genes on type 2 diabetes and related traits",

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 (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.",

author = "Billings, {Liana K.} and Hsu, {Yi Hsiang} and Ackerman, {Rachel J.} and Jos{\'e}e Dupuis and Voight, {Benjamin F.} and Rasmussen-Torvik, {Laura J.} and Serge Hercberg and Mark Lathrop and Daniel Barnes and Claudia Langenberg and Jennie Hui and Mao Fu and Nabila Bouatia-Naji and Cecile Lecoeur and Ping An and Magnusson, {Patrik K.} and Ida Surakka and Samuli Ripatti and Lene Christiansen and Christine Dalg{\aa}rd and Lasse Folkersen and Elin Grundberg and Per Eriksson and Jaakko Kaprio and Kyvik, {Kirsten Ohm} and Pedersen, {Nancy L.} and Borecki, {Ingrid B.} and Province, {Michael A.} and Beverley Balkau and Philippe Froguel and Shuldiner, {Alan R.} and Palmer, {Lyle J.} and Nick Wareham and Pierre Meneton and Toby Johnson and Pankow, {James S.} and David Karasik and Meigs, {James B.} and Kiel, {Douglas P.} and Florez, {Jose C.}",

year = "2012",

month = aug,

doi = "https://doi.org/10.2337/db11-1515",

language = "الإنجليزيّة",

volume = "61",

pages = "2176--2186",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "8",

}

Billings, LK, Hsu, YH, Ackerman, RJ, Dupuis, J, Voight, BF, Rasmussen-Torvik, LJ, Hercberg, S, Lathrop, M, Barnes, D, Langenberg, C, Hui, J, Fu, M, Bouatia-Naji, N, Lecoeur, C, An, P, Magnusson, PK, Surakka, I, Ripatti, S, Christiansen, L, Dalgård, C, Folkersen, L, Grundberg, E, Eriksson, P, Kaprio, J, Kyvik, KO, Pedersen, NL, Borecki, IB, Province, MA, Balkau, B, Froguel, P, Shuldiner, AR, Palmer, LJ, Wareham, N, Meneton, P, Johnson, T, Pankow, JS, Karasik, D, Meigs, JB, Kiel, DP & Florez, JC 2012, 'Impact of common variation in bone-related genes on type 2 diabetes and related traits', Diabetes, vol. 61, no. 8, pp. 2176-2186. https://doi.org/10.2337/db11-1515

TY - JOUR

T1 - Impact of common variation in bone-related genes on type 2 diabetes and related traits

AU - Billings, Liana K.

AU - Hsu, Yi Hsiang

AU - Ackerman, Rachel J.

AU - Dupuis, Josée

AU - Voight, Benjamin F.

AU - Rasmussen-Torvik, Laura J.

AU - Hercberg, Serge

AU - Lathrop, Mark

AU - Barnes, Daniel

AU - Langenberg, Claudia

AU - Hui, Jennie

AU - Fu, Mao

AU - Bouatia-Naji, Nabila

AU - Lecoeur, Cecile

AU - An, Ping

AU - Magnusson, Patrik K.

AU - Surakka, Ida

AU - Ripatti, Samuli

AU - Christiansen, Lene

AU - Dalgård, Christine

AU - Folkersen, Lasse

AU - Grundberg, Elin

AU - Eriksson, Per

AU - Kaprio, Jaakko

AU - Kyvik, Kirsten Ohm

AU - Pedersen, Nancy L.

AU - Borecki, Ingrid B.

AU - Province, Michael A.

AU - Balkau, Beverley

AU - Froguel, Philippe

AU - Shuldiner, Alan R.

AU - Palmer, Lyle J.

AU - Wareham, Nick

AU - Meneton, Pierre

AU - Johnson, Toby

AU - Pankow, James S.

AU - Karasik, David

AU - Meigs, James B.

AU - Kiel, Douglas P.

AU - Florez, Jose C.

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864387123&partnerID=8YFLogxK

U2 - https://doi.org/10.2337/db11-1515

DO - https://doi.org/10.2337/db11-1515

M3 - مقالة

C2 - 22698912

SN - 0012-1797

VL - 61

SP - 2176

EP - 2186

JO - Diabetes

JF - Diabetes

IS - 8

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this