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Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.
Medina-Gomez, Carolina; Mullin, Benjamin H; Chesi, Alessandra; Prijatelj, Vid; Kemp, John P; Shochat-Carvalho, Chen; Trajanoska, Katerina; Wang, Carol; Joro, Raimo; Evans, Tavia E; Schraut, Katharina E; Li-Gao, Ruifang; Ahluwalia, Tarunveer S; Zillikens, M Carola; Zhu, Kun; Mook-Kanamori, Dennis O; Evans, Daniel S; Nethander, Maria; Knol, Maria J; Thorleifsson, Gudmar; Prokic, Ivana; Zemel, Babette; Broer, Linda; McGuigan, Fiona E; van Schoor, Natasja M; Reppe, Sjur; Pawlak, Mikolaj A; Ralston, Stuart H; van der Velde, Nathalie; Lorentzon, Mattias; Stefansson, Kari; Adams, Hieab H H; Wilson, Scott G; Ikram, M Arfan; Walsh, John P; Lakka, Timo A; Gautvik, Kaare M; Wilson, James F; Orwoll, Eric S; van Duijn, Cornelia M; Bønnelykke, Klaus; Uitterlinden, Andre G; Styrkársdóttir, Unnur; Akesson, Kristina E; Spector, Timothy D; Tobias, Jonathan H; Ohlsson, Claes; Felix, Janine F; Bisgaard, Hans; Grant, Struan F A.
Affiliation
  • Medina-Gomez C; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Mullin BH; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
  • Chesi A; School of Biomedical Sciences, University of Western Australia, Nedlands, WA, 6009, Australia.
  • Prijatelj V; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
  • Kemp JP; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Shochat-Carvalho C; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
  • Trajanoska K; The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, 4102, Australia.
  • Wang C; MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.
  • Joro R; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.
  • Evans TE; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Schraut KE; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Li-Gao R; School of Women's and Infants' Health, University of Western Australia, Crawley, WA, 6009, Australia.
  • Ahluwalia TS; Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, 70211, Finland.
  • Zillikens MC; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Zhu K; Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Mook-Kanamori DO; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH16 4UX, Scotland.
  • Evans DS; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH8 9AG, Scotland.
  • Nethander M; Department of Clinical Epidemiology, Leiden University Medical Centre, 2333 ZA, Leiden, The Netherlands.
  • Knol MJ; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820, Denmark.
  • Thorleifsson G; Steno Diabetes Center Copenhagen, Herlev, 2820, Denmark.
  • Prokic I; The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Zemel B; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Broer L; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.
  • McGuigan FE; Medical School, University of Western Australia, Perth, WA, 6009, Australia.
  • van Schoor NM; Department of Clinical Epidemiology, Leiden University Medical Centre, 2333 ZA, Leiden, The Netherlands.
  • Reppe S; Department of Public Health and Primary Care, Leiden University Medical Centre, 2333 ZA, Leiden, The Netherlands.
  • Pawlak MA; California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA.
  • Ralston SH; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
  • van der Velde N; Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
  • Lorentzon M; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Stefansson K; deCODE Genetics/Amgen, Reykjavik, IC-101, Iceland.
  • Adams HHH; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Wilson SG; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Ikram MA; Division of GI, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
  • Walsh JP; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Lakka TA; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, 205 02, Malmö, Sweden.
  • Gautvik KM; Department of Epidemiology and Data Science, Amsterdam UMC, 1081 HV, Amsterdam, The Netherlands.
  • Wilson JF; Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0372, Oslo, Norway.
  • Orwoll ES; Department of Medical Biochemistry, Oslo University Hospital, 0372, Oslo, Norway.
  • van Duijn CM; Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, 0456, Oslo, Norway.
  • Bønnelykke K; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Uitterlinden AG; Department of Neurology, Poznan University of Medical Sciences, 61-701, Poznan, Poland.
  • Styrkársdóttir U; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, Scotland.
  • Akesson KE; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Spector TD; Department of Geriatric Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, 1105 AZ, Amsterdam, The Netherlands.
  • Tobias JH; Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
  • Ohlsson C; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, 3000, Australia.
  • Felix JF; deCODE Genetics/Amgen, Reykjavik, IC-101, Iceland.
  • Bisgaard H; Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
  • Grant SFA; Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands.
Commun Biol ; 6(1): 691, 2023 07 04.
Article in En | MEDLINE | ID: mdl-37402774
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Density / Craniosynostoses Type of study: Prognostic_studies / Systematic_reviews Limits: Animals Language: En Journal: Commun Biol Year: 2023 Document type: Article Affiliation country: Países Bajos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Density / Craniosynostoses Type of study: Prognostic_studies / Systematic_reviews Limits: Animals Language: En Journal: Commun Biol Year: 2023 Document type: Article Affiliation country: Países Bajos