Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: The Chungju Metabolic Disease Cohort (CMC) study
ENDOCRINE JOURNAL
Authors: Park, Se Eun; Oh, Ki Won; Lee, Won Young; Baek, Ki Hyun; Yoon, Kun Ho; Son, Ho Young; Lee, Won Chul; Kang, Moo Il
Abstract
In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESRI rs2941740, TNFRSF IIB rs3134070, TNFRSF IIB rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSFII rs9594782, and F027,1 rs10048146; and the association between these SNPs and bone metabolismrelated markers was assessed. Two SNPs, TNFSF11 rs2277438 and Falai rs1004816, were associated with lumbar spine BMD. TNFSFII rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and NHF2C rs1366594 and ESRI rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2Crs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSFIIB rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESRI, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.
Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies
NATURE GENETICS
Authors: Rivadeneira, Fernando; Styrkarsdottir, Unnur; Estrada, Karol; Halldorsson, Bjarni V.; Hsu, Yi-Hsiang; Richards, J. Brent; Zillikens, M. Carola; Kavvoura, Fotini K.; Amin, Najaf; Aulchenko, Yurii S.; Cupples, L. Adrienne; Deloukas, Panagiotis; Demissie, Serkalem; Grundberg, Elin; Hofman, Albert; Kong, Augustine; Karasik, David; van Meurs, Joyce B.; Oostra, Ben; Pastinen, Tomi; Pols, Huibert A. P.; Sigurdsson, Gunnar; Soranzo, Nicole; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Williams, Frances M. K.; Wilson, Scott G.; Zhou, Yanhua; Ralston, Stuart H.; van Duijn, Cornelia M.; Spector, Timothy; Kiel, Douglas P.; Stefansson, Kari; Ioannidis, John P. A.; Uitterlinden, Andre G.
Abstract
Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
COA
Publication 
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