SynthesisNature genetics2012
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 728 papers, 10 of them syntheses that pooled it.
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728citing papers in PubMed, 10 pooled it
83.4field-weighted citation impact, top 1% of its field
What it found
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Who cites it
728 citing papers in PubMed, 10 syntheses or guidelines pooled it, 1,211 citations in OpenAlex.
- Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.Clinical reviews in allergy & immunology · 2024Pooled it
- Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Pooled it
- Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.Communications biology · 2023Pooled it
- Meta-analysis of erosive hand osteoarthritis identifies four common variants that associate with relatively large effect.Annals of the rheumatic diseases · 2023Pooled it
- Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.Cell reports. Medicine · 2022Pooled it
- Using a Polygenic Score to Predict the Risk of Developing Primary Osteoporosis.International journal of molecular sciences · 2022Pooled it
- Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index.International journal of epidemiology · 2022Pooled it
- Endogenous DHEAS Is Causally Linked With Lumbar Spine Bone Mineral Density and Forearm Fractures in Women.The Journal of clinical endocrinology and metabolism · 2022Pooled it
- A multiethnic whole genome sequencing study to identify novel loci for bone mineral density.Human molecular genetics · 2022Pooled it
- Associations of osteoprotegerin (OPG) TNFRSF11B gene polymorphisms with risk of fractures in older adult populations: meta-analysis of genetic and genome-wide association studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Pooled it
- DNA methylation signatures in skeletal muscle associated with physical function in healthy older adults.GeroScience · 2026Article
- BICC1 attenuates oxidative stress-induced osteogenic injury via regulation of the PDK/PDH axis in MC3T3-E1 cells.Journal of bioenergetics and biomembranes · 2026Article
- 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
- Association between body composition and bone mineral density in young and middle-aged adults.BMC endocrine disorders · 2026Article
- A Bone-Protective Role for IFN-γ? Evidence from Genetic Association and Osteoblast Functional Assays in Postmenopausal Osteoporosis.International journal of molecular sciences · 2026Article
- Region-specific cortico-striatal transcriptomic remodeling following early postnatal dopaminergic disturbance.bioRxiv : the preprint server for biology · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- Identification of ephrin-A1-EphA2 signalling as a potential target for fracture prevention.Nature communications · 2026Article
- Integrative Harmonization of Phenotypic and Genomic Data Improves Bone Mineral Density Prediction in Multi-Study Osteoporosis Research.Genetic epidemiology · 2026Article
- Article
668 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
181 authors at 20 institutions in 23 countries.
Karol EstradaDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Unnur Styrkarsdottir
Evangelos Evangelou
Yi-Hsiang Hsu
Emma L Duncan
Evangelia E Ntzani
Ling Oei
Omar M E Albagha
Najaf Amin
John P Kemp
Daniel L Koller
Guo Li
Ching-Ti Liu
Ryan L Minster
Alireza Moayyeri
Liesbeth Vandenput
Dana Willner
Su-Mei Xiao
Laura M Yerges-Armstrong
Hou-Feng Zheng
Nerea Alonso
Joel Eriksson
Candace M Kammerer
Stephen K Kaptoge
Paul J Leo
Gudmar Thorleifsson
Scott G Wilson
James F Wilson
Ville Aalto
Markku Alen
Aaron K Aragaki
Thor Aspelund
Jacqueline R Center
Zoe Dailiana
David J Duggan
Melissa Garcia
Natàlia Garcia-Giralt
Sylvie Giroux
Göran Hallmans
Lynne J Hocking
Lise Bjerre Husted
Karen A Jameson
Rita Khusainova
Ghi Su Kim
Charles Kooperberg
Theodora Koromila
Marcin Kruk
Marika Laaksonen
Andrea Z Lacroix
Seung Hun Lee
Ping C Leung
Joshua R Lewis
Laura Masi
Simona Mencej-Bedrac
Tuan V Nguyen
Xavier Nogues
Millan S Patel
Janez Prezelj
Lynda M Rose
Serena Scollen
Kristin Siggeirsdottir
Albert V Smith
Olle Svensson
Stella Trompet
Olivia Trummer
Natasja M van Schoor
Jean Woo
Kun Zhu
Susana Balcells
Maria Luisa Brandi
Brendan M Buckley
Sulin Cheng
Claus Christiansen
Cyrus Cooper
George Dedoussis
Ian Ford
Morten Frost
David Goltzman
Jesús González-Macías
Mika Kähönen
Magnus Karlsson
Elza Khusnutdinova
Jung-Min Koh
Panagoula Kollia
Bente Lomholt Langdahl
William D Leslie
Paul Lips
Östen Ljunggren
Roman S Lorenc
Janja Marc
Dan Mellström
Barbara Obermayer-Pietsch
José M Olmos
Ulrika Pettersson-Kymmer
David M Reid
José A Riancho
Paul M Ridker
François Rousseau
P Eline Slagboom
Nelson L S Tang
Roser Urreizti
Wim Van Hul
Jorma Viikari
María T Zarrabeitia
Yurii S Aulchenko
Martha Castano-Betancourt
Elin Grundberg
Lizbeth Herrera
Thorvaldur Ingvarsson
Hrefna Johannsdottir
Tony Kwan
Rui Li
Robert Luben
Carolina Medina-Gómez
Stefan Th Palsson
Sjur Reppe
Jerome I Rotter
Gunnar Sigurdsson
Joyce B J van Meurs
Dominique Verlaan
Frances M K Williams
Andrew R Wood
Yanhua Zhou
Kaare M Gautvik
Tomi Pastinen
Soumya Raychaudhuri
Jane A Cauley
Daniel I Chasman
Graeme R Clark
Steven R Cummings
Patrick Danoy
Elaine M Dennison
Richard Eastell
John A Eisman
Vilmundur Gudnason
Albert Hofman
Rebecca D Jackson
Graeme Jones
J Wouter Jukema
Kay-Tee Khaw
Terho Lehtimäki
Yongmei Liu
Mattias Lorentzon
Eugene McCloskey
Braxton D Mitchell
Kannabiran Nandakumar
Geoffrey C Nicholson
Ben A Oostra
Munro Peacock
Huibert A P Pols
Richard L Prince
Olli Raitakari
Ian R Reid
John Robbins
Philip N Sambrook
Pak Chung Sham
Alan R Shuldiner
Frances A Tylavsky
Cornelia M van Duijn
Nick J Wareham
L Adrienne Cupples
Michael J Econs
David M Evans
Tamara B Harris
Annie Wai Chee Kung
Bruce M Psaty
Jonathan Reeve
Timothy D Spector
Elizabeth A Streeten
M Carola Zillikens
Unnur Thorsteinsdottir
Claes Ohlsson
David Karasik
J Brent Richards
Matthew A Brown
Kari Stefansson
André G Uitterlinden
Stuart H Ralston
John P A Ioannidis
Douglas P Kiel
Fernando Rivadeneira
Erasmus MC · NLMcGill University · CAThe University of Queensland · AUUniversity of Cambridge · GBNetherlands Consortium for Healthy Ageing · NLUniversity of Gothenburg · SEUniversity of Iceland · ISBrigham and Women's Hospital · USdeCODE Genetics (Iceland) · ISUniversidad de Cantabria · ESUniversity of Maryland, Baltimore · USBoston University · USChinese University of Hong Kong · HKFred Hutch Cancer Center · USHarvard University · USIcelandic Heart Association · ISIndiana University School of MedicineInstitute of Genetics and Cancer · GBKing's College London · GBMRC Lifecourse Epidemiology Unit · GB
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MWomen's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2MZOSUQUIDAR TRIHYDROCHLORIDE DURING CONVENTIONAL INDUCTION AND POST-REMISSIONM01RR000750 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI STORNIOLO, ANNA · 1985 to 2008
$25.5MPharmacogenomics and Risk of Cardiovascular DiseaseU01HL069757 · NHLBI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI KRAUSS, RONALD M · 2001 to 2009
$24.7MGENETICS OF BONE LOSS AND BONE STRENGTH IN WOMEN &MENP01AG018397 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI ECONS, MICHAEL J · 2000 to 2010
$19.1MResearch BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3MRISK FACTORS FOR VERTEBRAL FRACTURE AND BONE LOSSR01AR041398 · NIAMS · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI KIEL, DOUGLAS P. · 1991 to 2025
$16.1MPharmacogenomics and Risk of Cardiovascular DiseaseU19HL069757 · NHLBI · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI KRAUSS, RONALD M · 2010 to 2014
$12.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MArthritis Research UK 15389Arthritis Research UK 17539British Heart Foundation RG/08/014/24067Chief Scientist Office CZB/4/710CIHR 86748Intramural NIH HHSMedical Research Council 254627Medical Research Council 303169Medical Research Council 572604Medical Research Council G0401527Medical Research Council G0600705Medical Research Council G0800582Medical Research Council G1000143Medical Research Council G9321536Medical Research Council G9800062Medical Research Council MC_PC_U127561128Medical Research Council MC_U147585824Medical Research Council MC_UP_A620_1014NCATS NIH HHS UL1 TR000124NCI NIH HHS CA 047988NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA047988NCRR NIH HHS M01 RR000425NCRR NIH HHS M01 RR000750NCRR NIH HHS M01-RR00425NCRR NIH HHS M01 RR-00750NHGRI NIH HHS HHSN268200782096CNHLBI NIH HHS HL 043851NHLBI NIH HHS HL075366NHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS HL69757NHLBI NIH HHS N01 HC015103NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC035129NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC075150NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085084NHLBI NIH HHS N01 HC085085NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC-55222,NHLBI NIH HHS N01-HC-75150NHLBI NIH HHS N01-HC-85079NHLBI NIH HHS N01-HC-85086NHLBI NIH HHS N01-HC-85239NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL075366NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL088119NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL069757NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL084756NHLBI NIH HHS U19 HL069757NIAMS NIH HHS F32 AR059469NIAMS NIH HHS K08 AR055688NIAMS NIH HHS R01 AR041398NIAMS NIH HHS R01 AR046838NIAMS NIH HHS R01AR046838NIAMS NIH HHS R01 AR 050066NIAMS NIH HHS R01 AR050066NIA NIH HHS 1R01AG032098NIA NIH HHS AG-023629NIA NIH HHS AG-027058NIA NIH HHS AG-20098NIA NIH HHS N01 AG012100NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062103NIA NIH HHS N01 AG062106NIA NIH HHS P01 AG018397NIA NIH HHS P01 AG-18397NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG018728NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG027058NIA NIH HHS R01 AG032098NIA NIH HHS R01 AG041517NIA NIH HHS R01 AG18728NIA NIH HHS R01 AR/AG 41398NIA NIH HHS R56 AG020098NIA NIH HHS R56 AG023629NIA NIH HHS T32 AG000262NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488Wellcome Trust
Abstract
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Indexed as
Quantitative Trait LociBone DensityComputational BiologyExtracellular Matrix ProteinsFemaleFemur NeckFractures, BoneGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeGlycoproteinsHumansIntercellular Signaling Peptides and ProteinsLow Density Lipoprotein Receptor-Related Protein-5Lumbar VertebraeDKK1 protein, humanExtracellular Matrix ProteinsGlycoproteinsIntercellular Signaling Peptides and ProteinsLow Density Lipoprotein Receptor-Related Protein-5LRP5 protein, humanMEPE protein, humanMitochondrial Membrane Transport ProteinsPhosphoproteinsSLC25A13 protein, humanSpectrinSPTBN1 protein, human
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