GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.
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Stefansson, Olafur A
Lund, Sigrun H
Agustsdottir, Arna B
Halldorsson, Gisli H
Ivarsdottir, Erna V
Boer, Cindy G
Leung, Jason C S
Tang, Nelson L S
Kwok, Timothy C Y
Lee, Jenny S W
Ho, Suzanne C
Center, Jacqueline R
Lee, Seung Hun
Lohmander, L Stefan
Ho-Pham, Lan T
Nguyen, Tuan V
Eisman, John A
van Meurs, Joyce
Uitterlinden, Andre G
Norddahl, Gudmundur L
Gudbjartsson, Daniel F
MetadataShow full item record
CitationGWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. 2019, 10(1):2054
AbstractBone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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