{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:34:16Z","timestamp":1783650856470,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Using adult identified bone mineral density (BMD) loci, we calculated genetic risk scores (GRS) to determine if they were associated with changes in BMD during childhood. Longitudinal data from the Bone Mineral Density in Childhood Study were analyzed (N\u2009=\u2009798, 54% female, all European ancestry). Participants had up to 6 annual dual energy X-ray scans, from which areal BMD (aBMD) Z-scores for the spine, total hip, and femoral neck were estimated, as well as total body less head bone mineral content (TBLH-BMC) Z-scores. Sixty-three single-nucleotide polymorphisms (SNPs) were genotyped, and the percentage of BMD-lowering alleles carried was calculated (overall adult GRS). Subtype GRS that include SNPs associated with fracture risk, pediatric BMD, WNT signaling, RANK-RANKL-OPG, and mesenchymal stem cell differentiation were also calculated. Linear mixed effects models were used to test associations between each GRS and bone Z-scores, and if any association differed by sex and\/or chronological age. The overall adult, fracture, and WNT signaling GRS were associated with lower Z-scores (eg, spine aBMD Z-score: \u03b2adult\u2009=\u2009\u20130.04, p\u2009=\u20093.4\u2009\u00d7\u200910\u22127; \u03b2fracture\u2009=\u2009\u20130.02, p\u2009=\u20098.9\u2009\u00d7\u200910\u22126; \u03b2WNT\u2009=\u2009\u20130.01, p\u2009=\u20093.9\u2009\u00d7\u200910\u22124). The overall adult GRS was more strongly associated with lower Z-scores in females (p-interaction\u2009\u2264\u20090.05 for all sites). The fracture GRS was more strongly associated with lower Z-scores with increasing age (p-interaction\u2009\u2264\u20090.05 for all sites). The WNT GRS associations remained consistent for both sexes and all ages (p-interaction\u2009&amp;gt;\u20090.05 for all sites). The RANK-RANKL-OPG GRS was more strongly associated in females with increasing age (p-interaction\u2009&amp;lt;\u20090.05 for all sites). The mesenchymal stem cell GRS was associated with lower total hip and femoral neck Z-scores, in both boys and girls, across all ages. No associations were observed between the pediatric GRS and bone Z-scores. In conclusion, adult identified BMD loci associated with BMD and BMC in the pediatric setting, especially in females and in loci involved in fracture risk and WNT signaling. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2744","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T09:31:15Z","timestamp":1447752675000},"page":"789-795","source":"Crossref","is-referenced-by-count":30,"title":["Genetic Risk Scores Implicated in Adult Bone Fragility Associate With Pediatric Bone Density"],"prefix":"10.1093","volume":"31","author":[{"given":"Jonathan A","family":"Mitchell","sequence":"first","affiliation":[{"name":"Department of PediatricsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaPAUSA"},{"name":"Division of GastroenterologyHepatology and Nutrition, The Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Chesi","sequence":"additional","affiliation":[{"name":"Division of Human GeneticsChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okan","family":"Elci","sequence":"additional","affiliation":[{"name":"Biostatistics and Data Management CoreChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana E","family":"McCormack","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and DiabetesThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"},{"name":"Department of PediatricsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sani M","family":"Roy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and DiabetesThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi J","family":"Kalkwarf","sequence":"additional","affiliation":[{"name":"Division of GastroenterologyHepatology and Nutrition, Cincinnati Children's Hospital Medical CenterCincinnatiOHUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M","family":"Lappe","sequence":"additional","affiliation":[{"name":"Division of EndocrinologyDepartment of Medicine, Creighton UniversityOmahaNEUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Gilsanz","sequence":"additional","affiliation":[{"name":"Department of RadiologyChildren's Hospital Los AngelesLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon E","family":"Oberfield","sequence":"additional","affiliation":[{"name":"Division of Pediatric EndocrinologyDiabetes, and Metabolism, Department of Pediatrics, Columbia University Medical CenterNew YorkNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department of RadiologyUniversity of California San FranciscoSan FranciscoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and DiabetesThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"},{"name":"Department of PediatricsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Struan FA","family":"Grant","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and DiabetesThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"},{"name":"Division of Human GeneticsChildren's Hospital of PhiladelphiaPhiladelphiaPAUSA"},{"name":"Department of PediatricsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babette S","family":"Zemel","sequence":"additional","affiliation":[{"name":"Department of PediatricsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaPAUSA"},{"name":"Division of GastroenterologyHepatology and Nutrition, The Children's Hospital of PhiladelphiaPhiladelphiaPAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,17]]},"reference":[{"issue":"11","key":"2024021014175050200_jbmr2744-bib-0001","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1002\/jbmr.2269","article-title":"The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine","volume":"29","author":"Wright","year":"2014","journal-title":"J Bone Miner 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