SynthesisCommunications biology2023
Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.
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In one paragraph
Synthesis in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
–field-weighted citation impact
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Who cites it
12 citing papers in PubMed.
- Exploring the causal relationship and pathogenesis of intracranial aneurysms with osteoporosis based on Mendelian randomization and bioinformatics study.Journal of bone and mineral metabolism · 2026Article
- Mandibular Cortical Thickness Predicts Skull BMD in Adolescents.Calcified tissue international · 2026Article
- Endometriosis-associated bone loss: re-evaluating the potential role of systemic inflammation and hypoestrogenic therapies.Frontiers in global women's health · 2026Review
- Genetic and epidemiologic assessment of mandibular cortical indices and bone mineral density in peripubertal children: the Generation R study.Clinical oral investigations · 2025Article
- Genome-wide Association Studies of over 30,000 Samples with Bone Mineral Density at Multiple Skeletal Sites and Its Clinical Relevance.Genomics, proteomics & bioinformatics · 2025Article
- GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.Genome biology · 2025Article
- Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS.Communications biology · 2025Article
- GWAS-Informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.bioRxiv : the preprint server for biology · 2024Article
- Valid inference for machine learning-assisted genome-wide association studies.Nature genetics · 2024Article
- Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture.Frontiers in immunology · 2024Article
- Regulatory elements inGenetics in medicine open · 2024Article
- Zebrafish as a Model for Osteoporosis: Functional Validations of Genome-Wide Association Studies.Current osteoporosis reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
58 authors.
Carolina Medina-Gomez *Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0001-7999-5538
Benjamin H Mullin *Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.ORCID 0000-0003-0743-770X
Alessandra Chesi *Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Vid PrijateljDepartment of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-9463-3962
John P KempInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.ORCID 0000-0002-9105-2249
Chen Shochat-CarvalhoAzrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.
Katerina TrajanoskaDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Carol WangSchool of Women's and Infants' Health, University of Western Australia, Crawley, WA, 6009, Australia.
Raimo JoroInstitute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, 70211, Finland.
Tavia E EvansDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-2390-286X
Katharina E SchrautCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH16 4UX, Scotland.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Centre, 2333 ZA, Leiden, The Netherlands.
Tarunveer S AhluwaliaCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820, Denmark.ORCID 0000-0002-7464-3354
M Carola ZillikensDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0001-9186-3423
Kun ZhuDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.ORCID 0000-0002-8723-7574
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Centre, 2333 ZA, Leiden, The Netherlands.
Daniel S EvansCalifornia Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
Maria NethanderBioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.ORCID 0000-0003-3688-906X
Maria J KnolDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-3597-1531
Gudmar ThorleifssondeCODE Genetics/Amgen, Reykjavik, IC-101, Iceland.ORCID 0000-0003-4623-9087
Ivana ProkicDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-0370-1473
Babette ZemelDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.ORCID 0000-0002-6164-7348
Linda BroerDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-0011-123X
Fiona E McGuiganClinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, 205 02, Malmö, Sweden.
Natasja M van SchoorDepartment of Epidemiology and Data Science, Amsterdam UMC, 1081 HV, Amsterdam, The Netherlands.
Sjur ReppeDepartment of Plastic and Reconstructive Surgery, Oslo University Hospital, 0372, Oslo, Norway.ORCID 0000-0002-4330-5379
Mikolaj A PawlakDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-8607-0194
Stuart H RalstonCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, Scotland.ORCID 0000-0002-2804-7586
Nathalie van der VeldeDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Mattias LorentzonCenter for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
Kari StefanssondeCODE Genetics/Amgen, Reykjavik, IC-101, Iceland.
Hieab H H AdamsDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-3687-2508
Scott G WilsonDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.ORCID 0000-0002-0357-1373
M Arfan IkramDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-0372-8585
John P WalshDepartment of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
Timo A LakkaInstitute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, 70211, Finland.ORCID 0000-0002-9199-2871
Kaare M GautvikUnger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0456, Oslo, Norway.
James F WilsonCentre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH16 4UX, Scotland.ORCID 0000-0001-5751-9178
Eric S OrwollDepartment of Public Health & Preventive Medicine, Oregon Health & Science University, Portland, OR, OR97239, USA.ORCID 0000-0002-8520-7355
Cornelia M van DuijnDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-2374-9204
Klaus BønnelykkeCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820, Denmark.ORCID 0000-0003-2003-1018
Andre G UitterlindenDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-7276-3387
Unnur StyrkársdóttirdeCODE Genetics/Amgen, Reykjavik, IC-101, Iceland.ORCID 0000-0001-8146-8278
Kristina E AkessonClinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, 205 02, Malmö, Sweden.
Timothy D SpectorDepartment of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK.ORCID 0000-0002-9795-0365
Jonathan H TobiasMRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.
Claes OhlssonCenter for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.ORCID 0000-0002-9633-2805
Janine F FelixThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0002-9801-5774
Hans BisgaardCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820, Denmark.
Struan F A GrantDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
J Brent RichardsDepartment of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK.ORCID 0000-0002-3746-9086
David M EvansInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.ORCID 0000-0003-0663-4621
Bram van der EerdenDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.ORCID 0000-0003-4403-6497
Jeroen van de PeppelDepartment of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Cheryl Ackert-BicknellDepartment of Orthopedics, University of Colorado, Aurora, CO, 80045, USA.ORCID 0000-0003-4253-4775
David KarasikAzrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.ORCID 0000-0002-8826-0530
Erika KagueThe School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences, University of Bristol, Bristol, BS8 1TD, UK.ORCID 0000-0002-0266-9424
Fernando RivadeneiraDepartment of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands. f.rivadeneira@erasmusmc.nl.ORCID 0000-0001-9435-9441
Funding
Oregon Clinical and Translational Research InstituteUL1TR000128 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLISON, DAVID H · 2012 to 2015
$28.7MZIDOVUDINE VS 2',3'DIDEHYDRO-3'DEOXYTHYMIDINE IN CHILDRENM01RR000240 · NCRR · CHILDREN'S HOSP OF PHILADELPHIA · PI ALTSCHULER, STEVEN M · 1985 to 2006
$15.3MCTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR026314 · NCRR · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E. · 2009 to 2011
$14.3MOsteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3MGWAS in MrOS and SOFRC2AR058973 · NIAMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2009 to 2010
$5.7MIntegrative Resource to Develop Translational Strategies to Promote LongevityU24AG051129 · NIA · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON, EVANS, DANIEL SPENCER · 2015 to 2019
$5.3MOsteoporotic Fractures in Men (MrOS) - MinneapolisU01AG042145 · NIA · UNIVERSITY OF MINNESOTA · PI ENSRUD, KRISTINE · 2013 to 2019
$5.3MOsteporotic Fractures in Men (MrOS)- Admin CenterU01AG027810 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2006 to 2017
$5.1MGenomics of bone and body composition traits in childrenR01HD100406 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A, ZEMEL, BABETTE S · 2020 to 2024
$3.4MGenome Wide Association Study of Bone Mineral Accretion During ChildhoodR01HD058886 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI GRANT, STRUAN F A, ZEMEL, BABETTE S · 2010 to 2013
$3.1MOsteoporotic Fractures in Men (MrOS) - PortlandU01AG042124 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ORWOLL, ERIC S. · 2013 to 2019
$3.0MOsteoporatic Fractures in Men (MrOS)U01AG042168 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KADO, DEBORAH · 2013 to 2017
$3.0MMedical Research Council MC_UU_00007/10NCATS NIH HHS UL1 TR000128NCRR NIH HHS M01 RR000240NCRR NIH HHS UL1 RR026314NIAMS NIH HHS R01 AR051124NIAMS NIH HHS R21 AR060981NIAMS NIH HHS RC2 AR058973NIAMS NIH HHS U01 AR066160NIA NIH HHS U01 AG027810NIA NIH HHS U01 AG042124NIA NIH HHS U01 AG042139NIA NIH HHS U01 AG042140NIA NIH HHS U01 AG042143NIA NIH HHS U01 AG042145NIA NIH HHS U01 AG042168NICHD NIH HHS R01 HD058886NICHD NIH HHS R01 HD100406Wellcome Trust
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.
Indexed as
Bone DensityCraniosynostosesAnimalsGenome-Wide Association StudySkullTranscription FactorsZebrafishTranscription Factors
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