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A recently published genome-wide association study (GWAS) for estimated bone mineral density (eBMD) identified 1103 independent genome-wide significant association signals. Most of these variants are non-coding, suggesting that regulatory effects may drive many of the associations. To identify genes with a role in osteoporosis, we integrate the eBMD GWAS association results with those from our previous osteoclast expression quantitative trait locus (eQTL) dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identify sixty-nine significant\n                      <jats:italic>cis<\/jats:italic>\n                      -eQTL effects for eBMD GWAS variants after correction for multiple testing. We detect co-localisation of eBMD GWAS and osteoclast eQTL association signals for 21 of the 69 loci, implicating a number of genes including\n                      <jats:italic>CCR5<\/jats:italic>\n                      ,\n                      <jats:italic>ZBTB38<\/jats:italic>\n                      ,\n                      <jats:italic>CPE<\/jats:italic>\n                      ,\n                      <jats:italic>GNA12<\/jats:italic>\n                      ,\n                      <jats:italic>RIPK3<\/jats:italic>\n                      ,\n                      <jats:italic>IQGAP1<\/jats:italic>\n                      and\n                      <jats:italic>FLCN<\/jats:italic>\n                      . Summary-data-based Mendelian Randomisation analysis of the eBMD GWAS and osteoclast eQTL datasets identifies significant associations for 53 genes, with\n                      <jats:italic>TULP4<\/jats:italic>\n                      presenting as a strong candidate for pleiotropic effects on eBMD and gene expression in osteoclasts. By performing analysis using the GARFIELD software, we demonstrate significant enrichment of osteoporosis risk variants among high-confidence osteoclast eQTL across multiple GWAS\n                      <jats:italic>P<\/jats:italic>\n                      value thresholds. Mice lacking one of the genes of interest, the apoptosis\/necroptosis gene\n                      <jats:italic>RIPK3<\/jats:italic>\n                      , show disturbed bone micro-architecture and increased osteoclast number, highlighting a new biological pathway relevant to osteoporosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We utilise a unique osteoclast eQTL dataset to identify a number of potential effector genes for osteoporosis risk variants, which will help focus functional studies in this area.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13059-020-01997-2","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T08:03:08Z","timestamp":1585209788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts"],"prefix":"10.1186","volume":"21","author":[{"given":"Benjamin H.","family":"Mullin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tickner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Kenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby","family":"Mullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Dudbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan J.","family":"Pavlos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward S.","family":"Mocarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,26]]},"reference":[{"issue":"7675","key":"1997_CR1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","volume":"550","author":"A Battle","year":"2017","unstructured":"Battle A, Brown CD, Engelhardt BE, Montgomery SB. 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