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dc.contributor.authorWang, X.
dc.contributor.authorSalimi, S.
dc.contributor.authorDeng, Z.
dc.date.accessioned2019-06-05T18:28:18Z
dc.date.available2019-06-05T18:28:18Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85046834610&doi=10.1038%2fs41598-018-25272-4&partnerID=40&md5=b3641591945274204144e31fff6d41e9
dc.identifier.urihttp://hdl.handle.net/10713/9452
dc.description.abstractWnt1-inducible signaling pathway protein-1 (WISP1) is a novel target of the Wnt pathway for modulating osteogenesis and improving bone strength. However, it is not clear if genetic variants in the WISP1 region are associated with bone mineral density (BMD) in human. The aim of this study is to investigate the role of genetic variation in WISP1 gene as a determinant of BMD in 1,510 Old Order Amish (OOA). We performed regional association analysis of 58 tag variants within 5 kb upstream and downstream to WISP1 with BMD and found 5 variants that were associated with BMD at multiple skeletal sites (P values from 2.89 × 10−6 to 1.62 × 10−2), with some significant associations even after adjustment for multiple comparisons. To replicate these results in an independent dataset, we performed a look-up of BMD associations with these variants in European ancestry subjects from the large GEFOS Consortium and observed the nominal associations of two of these variants with BMD (P values: 0.031 to 0.048). In conclusion, we have demonstrated that genetic variants surrounding WISP1 are associated with BMD at multiple skeletal sites in the OOA, thus influencing osteoporosis risk. These results support a role for the WISP1 gene on influencing variation in BMD. Copyright 2018 The Author(s).en_US
dc.description.sponsorshipThis work was supported by research grants HL69313, DK54261, AG1872801, HL088119, AR046838, HL72515 from the National Institutes of Health, American Diabetes Association grant [7-12-CT-26], American Heart Association grant [17GRNT33440151], and the program of China Scholarships Council (No. 1410260006).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41598-018-25272-4en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofScientific Reports
dc.subjectgenetic variantsen_US
dc.subjectOld Order Amishen_US
dc.subjectWISP1en_US
dc.subject.meshBone Density--geneticsen_US
dc.subject.meshOsteoporosisen_US
dc.subject.meshRisk Factorsen_US
dc.titleEvaluation of WISP1 as a candidate gene for bone mineral density in the Old Order Amishen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-018-25272-4


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