{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T10:23:31Z","timestamp":1774347811329,"version":"3.50.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"the Natural Science Basic Research Plan in Shaanxi Province of China","award":["2021JCW-08"],"award-info":[{"award-number":["2021JCW-08"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"DOI":"10.1007\/s00223-026-01494-x","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:54:04Z","timestamp":1774335244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Large-Scale Multi-omics Polygenic Risk Score Analysis Identified Candidate Biomarkers Associated with Heel Bone Mineral Density"],"prefix":"10.1007","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-6901","authenticated-orcid":false,"given":"Xuena","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuyu","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenming","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boyue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingni","family":"Hui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bolun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"10","key":"1494_CR1","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1002\/jbmr.3757","volume":"34","author":"Q Zeng","year":"2019","unstructured":"Zeng Q et al (2019) The prevalence of osteoporosis in China, a Nationwide, multicenter DXA survey. J Bone Min Res 34(10):1789\u20131797","journal-title":"J Bone Min Res"},{"key":"1494_CR2","doi-asserted-by":"crossref","unstructured":"Brandi ML, Piscitelli P (2013) Epidemiology of osteoporosis and fragility Fractures. In Guglielmi G (Ed) Osteoporosis and bone densitometry measurements. Springer, Berlin Heidelberg, pp 1\u20134","DOI":"10.1007\/174_2012_747"},{"issue":"1","key":"1494_CR3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00421-018-4007-8","volume":"119","author":"AJ Herbert","year":"2019","unstructured":"Herbert AJ et al (2019) The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes. Eur J Appl Physiol 119(1):29\u201347","journal-title":"Eur J Appl Physiol"},{"issue":"2","key":"1494_CR4","doi-asserted-by":"publisher","first-page":"100847","DOI":"10.1016\/j.isci.2020.100847","volume":"23","author":"C Qiu","year":"2020","unstructured":"Qiu C et al (2020) Multi-omics data integration for identifying osteoporosis biomarkers and their biological interaction and causal mechanisms. iScience 23(2):100847","journal-title":"iScience"},{"key":"1494_CR5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jprot.2016.04.044","volume":"142","author":"Y Zeng","year":"2016","unstructured":"Zeng Y et al (2016) Quantitative proteomics and integrative network analysis identified novel genes and pathways related to osteoporosis. J Proteom 142:45\u201352","journal-title":"J Proteom"},{"issue":"6","key":"1494_CR6","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1080\/14737159.2023.2208750","volume":"23","author":"J Yang","year":"2023","unstructured":"Yang J, Wu J (2023) Discovery of potential biomarkers for osteoporosis diagnosis by individual omics and multi-omics technologies. Expert Rev Mol Diagn 23(6):505\u2013520","journal-title":"Expert Rev Mol Diagn"},{"key":"1494_CR7","doi-asserted-by":"publisher","first-page":"14357","DOI":"10.1038\/ncomms14357","volume":"8","author":"K Suhre","year":"2017","unstructured":"Suhre K et al (2017) Connecting genetic risk to disease end points through the human blood plasma proteome. Nat Commun 8:14357","journal-title":"Nat Commun"},{"issue":"1","key":"1494_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s10038-020-00842-5","volume":"66","author":"M Akiyama","year":"2021","unstructured":"Akiyama M (2021) Multi-omics study for interpretation of genome-wide association study. J Hum Genet 66(1):3\u201310","journal-title":"J Hum Genet"},{"issue":"6","key":"1494_CR9","doi-asserted-by":"publisher","first-page":"e1262","DOI":"10.1097\/SLA.0000000000005623","volume":"277","author":"AC De Roo","year":"2023","unstructured":"De Roo AC et al (2023) Polygenic risk prediction in diverticulitis. Ann Surg 277(6):e1262\u2013e1268","journal-title":"Ann Surg"},{"issue":"9","key":"1494_CR10","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1093\/bioinformatics\/btu848","volume":"31","author":"J Euesden","year":"2015","unstructured":"Euesden J, Lewis CM, O\u2019Reilly PF (2015) PRSice: polygenic risk score software. Bioinformatics 31(9):1466\u20131468","journal-title":"Bioinformatics"},{"issue":"7955","key":"1494_CR11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41586-023-05844-9","volume":"616","author":"Y Xu","year":"2023","unstructured":"Xu Y et al (2023) An atlas of genetic scores to predict multi-omic traits. Nature 616(7955):123\u2013131","journal-title":"Nature"},{"key":"1494_CR12","doi-asserted-by":"crossref","unstructured":"Lv H et al (2016) Metabolomics and its application in the development of discovering biomarkers for osteoporosis research. Int J Mol Sci, 17(12):2018","DOI":"10.3390\/ijms17122018"},{"issue":"10","key":"1494_CR13","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1038\/ng.3949","volume":"49","author":"JP Kemp","year":"2017","unstructured":"Kemp JP et al (2017) Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet 49(10):1468\u20131475","journal-title":"Nat Genet"},{"issue":"7","key":"1494_CR14","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1016\/j.clnu.2019.09.005","volume":"39","author":"S Yuan","year":"2020","unstructured":"Yuan S et al (2020) Plasma phospholipid fatty acids, bone mineral density and fracture risk: evidence from a Mendelian randomization study. Clin Nutr 39(7):2180\u20132186","journal-title":"Clin Nutr"},{"issue":"3","key":"1494_CR15","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow C et al (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12(3):e1001779","journal-title":"PLoS Med"},{"key":"1494_CR16","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1186\/1745-6215-15-363","volume":"15","author":"C Moore","year":"2014","unstructured":"Moore C et al (2014) The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial. Trials 15:363","journal-title":"Trials"},{"key":"1494_CR17","unstructured":"Sun BB et al (2022) Genetic regulation of the human plasma proteome in 54,306 UK Biobank participants. bioRxiv, : 2022.06.17.496443"},{"issue":"1","key":"1494_CR18","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41467-023-36231-7","volume":"14","author":"H Julkunen","year":"2023","unstructured":"Julkunen H et al (2023) Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK biobank. Nat Commun 14(1):604","journal-title":"Nat Commun"},{"issue":"2","key":"1494_CR19","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41588-018-0302-x","volume":"51","author":"JA Morris","year":"2019","unstructured":"Morris JA et al (2019) An atlas of genetic influences on osteoporosis in humans and mice. Nat Genet 51(2):258\u2013266","journal-title":"Nat Genet"},{"issue":"7708","key":"1494_CR20","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","volume":"558","author":"BB Sun","year":"2018","unstructured":"Sun BB et al (2018) Genomic atlas of the human plasma proteome. Nature 558(7708):73\u201379","journal-title":"Nature"},{"issue":"6","key":"1494_CR21","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/ng.2982","volume":"46","author":"SY Shin","year":"2014","unstructured":"Shin SY et al (2014) An atlas of genetic influences on human blood metabolites. Nat Genet 46(6):543\u2013550","journal-title":"Nat Genet"},{"issue":"2","key":"1494_CR22","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44(2):512\u2013525","journal-title":"Int J Epidemiol"},{"issue":"10","key":"1494_CR23","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1007\/s00198-023-06807-6","volume":"34","author":"G Huang","year":"2023","unstructured":"Huang G et al (2023) Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population. Osteoporos Int 34(10):1719\u20131727","journal-title":"Osteoporos Int"},{"issue":"11","key":"1494_CR24","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1161\/ATVBAHA.119.313056","volume":"39","author":"PA Mueller","year":"2019","unstructured":"Mueller PA et al (2019) Coronary artery disease Risk-Associated Plpp3 gene and its product lipid phosphate phosphatase 3 regulate experimental atherosclerosis. Arterioscler Thromb Vasc Biol 39(11):2261\u20132272","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"1494_CR25","doi-asserted-by":"publisher","first-page":"158715","DOI":"10.1016\/j.bbalip.2020.158715","volume":"1865","author":"CA Alioli","year":"2020","unstructured":"Alioli CA et al (2020) Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification. Biochim Biophys Acta Mol Cell Biol Lipids 1865(8):158715","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"issue":"8","key":"1494_CR26","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1111\/j.1601-183X.2008.00436.x","volume":"7","author":"P Pandey","year":"2008","unstructured":"Pandey P, Pradhan S, Mittal B (2008) LRP-associated protein gene (LRPAP1) and susceptibility to degenerative dementia. Genes Brain Behav 7(8):943\u2013950","journal-title":"Genes Brain Behav"},{"issue":"1","key":"1494_CR27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41413-024-00393-x","volume":"13","author":"M Alhashmi","year":"2025","unstructured":"Alhashmi M et al (2025) Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation. Bone Res 13(1):17","journal-title":"Bone Res"},{"key":"1494_CR28","doi-asserted-by":"publisher","first-page":"e24","DOI":"10.1017\/erm.2024.24","volume":"26","author":"J Zhang","year":"2024","unstructured":"Zhang J et al (2024) Repulsive guidance molecules b (RGMb): molecular mechanism, function and role in diseases. Expert Rev Mol Med 26:e24","journal-title":"Expert Rev Mol Med"},{"issue":"2","key":"1494_CR29","doi-asserted-by":"publisher","first-page":"e0316824","DOI":"10.1371\/journal.pone.0316824","volume":"20","author":"C Lu","year":"2025","unstructured":"Lu C et al (2025) Mendelian randomization analysis to identify potential drug targets for osteoarthritis. PLoS One 20(2):e0316824","journal-title":"PLoS ONE"},{"issue":"5","key":"1494_CR30","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41419-018-0596-8","volume":"9","author":"P Liu","year":"2018","unstructured":"Liu P et al (2018) Grail is involved in adipocyte differentiation and diet-induced obesity. Cell Death Dis 9(5):525","journal-title":"Cell Death Dis"},{"issue":"1","key":"1494_CR31","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1038\/s41467-025-57404-6","volume":"16","author":"Y Liu","year":"2025","unstructured":"Liu Y et al (2025) E3 ubiquitin ligase RNF128 promotes Lys63-linked polyubiquitination on SRB1 in macrophages and aggravates atherosclerosis. Nat Commun 16(1):2185","journal-title":"Nat Commun"},{"issue":"1","key":"1494_CR32","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s13018-022-03161-x","volume":"17","author":"Y Li","year":"2022","unstructured":"Li Y (2022) Association between obesity and bone mineral density in middle-aged adults. J Orthop Surg Res 17(1):268","journal-title":"J Orthop Surg Res"},{"issue":"1","key":"1494_CR33","doi-asserted-by":"publisher","first-page":"783","DOI":"10.3892\/mmr.2015.3472","volume":"12","author":"L Tian","year":"2015","unstructured":"Tian L, Yu X (2015) Lipid metabolism disorders and bone dysfunction\u2013interrelated and mutually regulated (review). Mol Med Rep 12(1):783\u2013794","journal-title":"Mol Med Rep"},{"issue":"2","key":"1494_CR34","doi-asserted-by":"publisher","first-page":"e13551","DOI":"10.1111\/acel.13551","volume":"21","author":"M Hu","year":"2022","unstructured":"Hu M et al (2022) NAP1L2 drives mesenchymal stem cell senescence and suppresses osteogenic differentiation. Aging Cell 21(2):e13551","journal-title":"Aging Cell"},{"key":"1494_CR35","doi-asserted-by":"crossref","unstructured":"Yin W, Li Z, Zhang W (2019) Modulation of bone and marrow niche by cholesterol. Nutrients, 11(6):1394","DOI":"10.3390\/nu11061394"},{"issue":"5","key":"1494_CR36","first-page":"1330","volume":"15","author":"S Hu","year":"2023","unstructured":"Hu S et al (2023) Associations between serum total cholesterol level and bone mineral density in older adults. Aging 15(5):1330\u20131342","journal-title":"Aging"},{"issue":"12","key":"1494_CR37","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1038\/aps.2011.135","volume":"32","author":"L You","year":"2011","unstructured":"You L et al (2011) High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats. Acta Pharmacol Sin 32(12):1498\u20131504","journal-title":"Acta Pharmacol Sin"},{"issue":"6","key":"1494_CR38","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s00774-011-0274-8","volume":"29","author":"EM Alissa","year":"2011","unstructured":"Alissa EM et al (2011) Effect of diet and lifestyle factors on bone health in postmenopausal women. J Bone Min Metab 29(6):725\u2013735","journal-title":"J Bone Min Metab"},{"issue":"6","key":"1494_CR39","first-page":"790","volume":"76","author":"D Ceruti","year":"2024","unstructured":"Ceruti D et al (2024) Vitamin D levels and lipid profile in children and adolescents: a tight correlation. Minerva Pediatr (Torino) 76(6):790\u2013802","journal-title":"Minerva Pediatr (Torino)"},{"issue":"1","key":"1494_CR40","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1186\/s12889-023-16447-4","volume":"23","author":"X Huang","year":"2023","unstructured":"Huang X et al (2023) Association between vitamin D deficiency and lipid profiles in overweight and obese adults: a systematic review and meta-analysis. BMC Public Health 23(1):1653","journal-title":"BMC Public Health"},{"issue":"4","key":"1494_CR41","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1210\/edrv.22.4.0437","volume":"22","author":"P Lips","year":"2001","unstructured":"Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22(4):477\u2013501","journal-title":"Endocr Rev"},{"issue":"5","key":"1494_CR42","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1002\/jbmr.1559","volume":"27","author":"KE Barbour","year":"2012","unstructured":"Barbour KE et al (2012) Inflammatory markers and the risk of hip fracture: the women\u2019s health initiative. J Bone Min Res 27(5):1167\u20131176","journal-title":"J Bone Min Res"}],"container-title":["Calcified Tissue International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-026-01494-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00223-026-01494-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-026-01494-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:54:08Z","timestamp":1774335248000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00223-026-01494-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1494"],"URL":"https:\/\/doi.org\/10.1007\/s00223-026-01494-x","relation":{},"ISSN":["1432-0827"],"issn-type":[{"value":"1432-0827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"18 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Xuena Yang, Huan Liu, Ke Xu, Dan He, Shiqiang Cheng, Chuyu Pan, Li Liu, Wenming Wei, Boyue Zhao, Jingni Hui, Yan Wen, Yumeng Jia, Bolun Cheng, Peng Xu and Feng Zhang declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"45"}}