{"entity": "researcher", "timestamp": "2026-04-12T02:46:16.453Z", "family": "Zillikens", "given": "M Carola", "initials": "MC", "orcid": "0000-0001-9186-3423", "affiliations": ["Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/8c71c257a4de4ac7b59381237a0fa500.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/8c71c257a4de4ac7b59381237a0fa500"}}, "publications": [{"entity": "publication", "iuid": "74e6bcf9f810455aafeb36c2253b4848", "links": {"self": {"href": "https://publications.scilifelab.se/publication/74e6bcf9f810455aafeb36c2253b4848.json"}, "display": {"href": "https://publications.scilifelab.se/publication/74e6bcf9f810455aafeb36c2253b4848"}}, "title": "Gene-based association analysis of a large patient cohort provides insights into genetics of atypical femur fractures.", "authors": [{"family": "Zhou", "given": "Wei", "initials": "W", "orcid": "0000-0002-6748-6303", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f7e9b3a6ffa45dba854cb6acf59739b.json"}}, {"family": "\u00c5s", "given": "Joel", "initials": "J"}, {"family": "Shore-Lorenti", "given": "Catherine", "initials": "C"}, {"family": "Nguyen", "given": "Hanh H", "initials": "HH", "orcid": "0000-0002-8846-6168", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a4cb30d23e54b8c8b328859ead81ba7.json"}}, {"family": "van de Laarschot", "given": "Denise M", "initials": "DM"}, {"family": "Sztal-Mazer", "given": "Shoshana", "initials": "S"}, {"family": "Grill", "given": "Vivian", "initials": "V"}, {"family": "Girgis", "given": "Christian M", "initials": "CM"}, {"family": "Stricker", "given": "Bruno H Ch", "initials": "BHC"}, {"family": "van der Eerden", "given": "Bram C J", "initials": "BCJ"}, {"family": "Thakker", "given": "Rajesh V", "initials": "RV"}, {"family": "Appelman-Dijkstra", "given": "Natasha M", "initials": "NM", "orcid": "0000-0001-5035-127X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f26fbf2e8d14f8ebf65acd9e22d7b41.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M"}, {"family": "Clifton-Bligh", "given": "Roderick J", "initials": "RJ"}, {"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Verkerk", "given": "Annemieke J M H", "initials": "AJMH"}, {"family": "van Rooij", "given": "Jeroen G J", "initials": "JGJ"}, {"family": "Ebeling", "given": "Peter R", "initials": "PR"}, {"family": "Zillikens", "given": "M Carola", "initials": "MC", "orcid": "0000-0001-9186-3423", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c71c257a4de4ac7b59381237a0fa500.json"}}], "type": "journal article", "published": "2024-09-02", "journal": {"title": "J. Bone Miner. Res.", "issn": "1523-4681", "volume": "39", "issue": "9", "pages": "1315-1326", "issn-l": "0884-0431"}, "abstract": "Several small genetic association studies have been conducted for atypical femur fracture (AFF) without replication of results. We assessed previously implicated and novel genes associated with AFFs in a larger set of unrelated AFF cases using whole exome sequencing (WES). We performed gene-based association analysis on 139 European AFF cases and 196 controls matched for bisphosphonate use. We tested all rare, protein-altering variants using both candidate gene and hypothesis-free approaches. In the latter, genes suggestively associated with AFFs (uncorrected p-values <.01) were investigated in a Swedish whole-genome sequencing replication study and assessed in 46 non-European cases. In the candidate gene analysis, PLOD2 showed a suggestive signal. The hypothesis-free approach revealed 10 tentative associations, with XRN2, SORD, and PLOD2 being the most likely candidates for AFF. XRN2 and PLOD2 showed consistent direction of effect estimates in the replication analysis, albeit not statistically significant. Three SNPs associated with SORD expression according to the GTEx portal were in linkage disequilibrium (R2 \u2265 0.2) with an SNP previously reported in a genome-wide association study of AFF. The prevalence of carriers of variants for both PLOD2 and SORD was higher in Asian versus European cases. While we did not identify genes enriched for damaging variants, we found suggestive evidence of a role for XRN2, PLOD2, and SORD, which requires further investigation. Our findings indicate that genetic factors responsible for AFFs are not widely shared among AFF cases. The study provides a stepping-stone for future larger genetic studies of AFF.", "doi": "10.1093/jbmr/zjae122", "pmid": "39126371", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11371903"}, {"db": "pii", "key": "7731319"}], "notes": [], "created": "2024-10-21T11:12:51.933Z", "modified": "2024-10-21T11:13:04.359Z"}, {"entity": "publication", "iuid": "818deda624df4b0f953c5d290a05ed4a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/818deda624df4b0f953c5d290a05ed4a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/818deda624df4b0f953c5d290a05ed4a"}}, "title": "Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.", "authors": [{"family": "Medina-Gomez", "given": "Carolina", "initials": "C", "orcid": "0000-0001-7999-5538", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1f97914d1c34f1f8190738c2d2e27b0.json"}}, {"family": "Mullin", "given": "Benjamin H", "initials": "BH", "orcid": "0000-0003-0743-770X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc36788ecbd64ce6a0d9ff3311c15e59.json"}}, {"family": "Chesi", "given": "Alessandra", "initials": "A"}, {"family": "Prijatelj", "given": "Vid", "initials": "V", "orcid": "0000-0002-9463-3962", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac480b4f7b964169a845cceaac252420.json"}}, {"family": "Kemp", "given": "John P", "initials": "JP", "orcid": "0000-0002-9105-2249", "researcher": {"href": "https://publications.scilifelab.se/researcher/405cc434238b46b1984a2f1d9999e37a.json"}}, {"family": "Shochat-Carvalho", "given": "Chen", "initials": "C"}, {"family": "Trajanoska", "given": "Katerina", "initials": "K"}, {"family": "Wang", "given": "Carol", "initials": "C"}, {"family": "Joro", "given": "Raimo", "initials": "R"}, {"family": "Evans", "given": "Tavia E", "initials": "TE", "orcid": "0000-0003-2390-286X", "researcher": {"href": "https://publications.scilifelab.se/researcher/253058dc9f2d4cd8b041d9fbea739f58.json"}}, {"family": "Schraut", "given": "Katharina E", "initials": "KE"}, {"family": "Li-Gao", "given": "Ruifang", "initials": "R"}, {"family": "Ahluwalia", "given": "Tarunveer S", "initials": "TS", "orcid": "0000-0002-7464-3354", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fde142189574b44a72155785763a327.json"}}, {"family": "Zillikens", "given": "M Carola", "initials": "MC", "orcid": "0000-0001-9186-3423", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c71c257a4de4ac7b59381237a0fa500.json"}}, {"family": "Zhu", "given": "Kun", "initials": "K", "orcid": "0000-0002-8723-7574", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2d598b0ca9b454b9c08d5596d58063c.json"}}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Evans", "given": "Daniel S", "initials": "DS"}, {"family": "Nethander", "given": "Maria", "initials": "M", "orcid": "0000-0003-3688-906X", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d61951f51c4d40bef24672866382cb.json"}}, {"family": "Knol", "given": "Maria J", "initials": "MJ", "orcid": "0000-0002-3597-1531", "researcher": {"href": "https://publications.scilifelab.se/researcher/0edb736bd840429bbb57ecd1b2924561.json"}}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G", "orcid": "0000-0003-4623-9087", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc2210fecc9043c6b901506d35ca33e0.json"}}, {"family": "Prokic", "given": "Ivana", "initials": "I", "orcid": "0000-0002-0370-1473", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba397832a2a043c58abc1242c1f5599c.json"}}, {"family": "Zemel", "given": "Babette", "initials": "B", "orcid": "0000-0002-6164-7348", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e365d159aec4d4691dfeef1cd3a014b.json"}}, {"family": "Broer", "given": "Linda", "initials": "L", "orcid": "0000-0003-0011-123X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c13301e242214773852a42c19b272289.json"}}, {"family": "McGuigan", "given": "Fiona E", "initials": "FE"}, {"family": "van Schoor", "given": "Natasja M", "initials": "NM"}, {"family": "Reppe", "given": "Sjur", "initials": "S", "orcid": "0000-0002-4330-5379", "researcher": {"href": "https://publications.scilifelab.se/researcher/559c6027c01a4c69914cd8c9438a32d7.json"}}, {"family": "Pawlak", "given": "Mikolaj A", "initials": "MA", "orcid": "0000-0002-8607-0194", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d66d43db71040c08faf598a4a23e6db.json"}}, {"family": "Ralston", "given": "Stuart H", "initials": "SH", "orcid": "0000-0002-2804-7586", "researcher": {"href": "https://publications.scilifelab.se/researcher/7363cc37bb8e406e8d37a9dd8ed6a4df.json"}}, {"family": "van der Velde", "given": "Nathalie", "initials": "N"}, {"family": "Lorentzon", "given": "Mattias", "initials": "M"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Adams", "given": "Hieab H H", "initials": "HHH", "orcid": "0000-0003-3687-2508", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab5c4744d60d4290a3a8a6b80c107f42.json"}}, {"family": "Wilson", "given": "Scott G", "initials": "SG", "orcid": "0000-0002-0357-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b292912e02d464f9e0bffa13136c017.json"}}, {"family": "Ikram", "given": "M Arfan", "initials": "MA", "orcid": "0000-0003-0372-8585", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ec81571f4a94af682b4e23526f87385.json"}}, {"family": "Walsh", "given": "John P", "initials": "JP"}, {"family": "Lakka", "given": "Timo A", "initials": "TA", "orcid": "0000-0002-9199-2871", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf0d612e609d4b4caeab4dfd8fa503e6.json"}}, {"family": "Gautvik", "given": "Kaare M", "initials": "KM"}, {"family": "Wilson", "given": "James F", "initials": "JF", "orcid": "0000-0001-5751-9178", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39e6e0f7210494cb4f80be0f7413b6f.json"}}, {"family": "Orwoll", "given": "Eric S", "initials": "ES", "orcid": "0000-0002-8520-7355", "researcher": {"href": "https://publications.scilifelab.se/researcher/a48a5abda98c4650bc1007cd53f95823.json"}}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM", "orcid": "0000-0002-2374-9204", "researcher": {"href": "https://publications.scilifelab.se/researcher/354ccf94e95f40da96e61c89a0a60adb.json"}}, {"family": "B\u00f8nnelykke", "given": "Klaus", "initials": "K", "orcid": "0000-0003-2003-1018", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e0992f23e69443c8bf08589711cb9b9.json"}}, {"family": "Uitterlinden", "given": "Andre G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Styrk\u00e1rsd\u00f3ttir", "given": "Unnur", "initials": "U", "orcid": "0000-0001-8146-8278", "researcher": {"href": "https://publications.scilifelab.se/researcher/327b14e1055744e8976d926ddaa4d502.json"}}, {"family": "Akesson", "given": "Kristina E", "initials": "KE"}, {"family": "Spector", "given": "Timothy D", "initials": "TD", "orcid": "0000-0002-9795-0365", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3b149961364ccbb448a8cc3cdd6687.json"}}, {"family": "Tobias", "given": "Jonathan H", "initials": "JH"}, {"family": "Ohlsson", "given": "Claes", "initials": "C", "orcid": "0000-0002-9633-2805", "researcher": {"href": "https://publications.scilifelab.se/researcher/995dac358caa4a169fc889b7a3eef44a.json"}}, {"family": "Felix", "given": "Janine F", "initials": "JF", "orcid": "0000-0002-9801-5774", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4482378cb24a9f832729f7004a41bf.json"}}, {"family": "Bisgaard", "given": "Hans", "initials": "H"}, {"family": "Grant", "given": "Struan F A", "initials": "SFA"}, {"family": "Richards", "given": "J Brent", "initials": "JB", "orcid": "0000-0002-3746-9086", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c20c901fd041c194dae79b29b94ec2.json"}}, {"family": "Evans", "given": "David M", "initials": "DM", "orcid": "0000-0003-0663-4621", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b9b78a6c5b94bf18b798318935f62fd.json"}}, {"family": "van der Eerden", "given": "Bram", "initials": "B", "orcid": "0000-0003-4403-6497", "researcher": {"href": "https://publications.scilifelab.se/researcher/42514d51463941c5aad5083d181f0fe2.json"}}, {"family": "van de Peppel", "given": "Jeroen", "initials": "J"}, {"family": "Ackert-Bicknell", "given": "Cheryl", "initials": "C", "orcid": "0000-0003-4253-4775", "researcher": {"href": "https://publications.scilifelab.se/researcher/c843d9e827da46be81741184b57a4e38.json"}}, {"family": "Karasik", "given": "David", "initials": "D", "orcid": "0000-0002-8826-0530", "researcher": {"href": "https://publications.scilifelab.se/researcher/309cc98072424c52a29438620f03bfa0.json"}}, {"family": "Kague", "given": "Erika", "initials": "E", "orcid": "0000-0002-0266-9424", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5eaa107d04bb494e2567e66d75f71.json"}}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F", "orcid": "0000-0001-9435-9441", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8894904d3cf4671a2e563169829322a.json"}}], "type": "meta-analysis", "published": "2023-07-04", "journal": {"title": "Commun Biol", "issn": "2399-3642", "issn-l": "2399-3642", "volume": "6", "issue": "1", "pages": "691"}, "abstract": "Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.", "doi": "10.1038/s42003-023-04869-0", "pmid": "37402774", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10319806"}, {"db": "pii", "key": "10.1038/s42003-023-04869-0"}], "notes": [], "created": "2023-11-30T22:35:09.520Z", "modified": "2023-11-30T22:36:33.714Z"}]}