Impact of common variation in bone-related genes on type 2 diabetes and related traits.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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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, MAGIC Investigators, DIAGRAM + Consortium, MuTHER Consortium, ASCOT Investigators, GEFOS Consortium, 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, Meigs James B, Kiel Douglas P, Florez Jose C
Аннотация
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.