2.50
Hdl Handle:
http://hdl.handle.net/2336/84841
Title:
Multiple genetic loci for bone mineral density and fractures
Authors:
Styrkarsdottir, Unnur; Halldorsson, Bjarni V; Gretarsdottir, Solveig; Gudbjartsson, Daniel F; Walters, G Bragi; Ingvarsson, Thorvaldur; Jonsdottir, Thorbjorg; Saemundsdottir, Jona; Center, Jacqueline R; Nguyen, Tuan V; Bagger, Yu; Gulcher, Jeffrey R; Eisman, John A; Christiansen, Claus; Sigurdsson, Gunnar; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari
Citation:
N. Engl. J. Med. 2008, 358(22):2355-65
Issue Date:
29-May-2008
Abstract:
BACKGROUND: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. METHODS: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). RESULTS: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10(-7) to 2.0x10(-21)). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-kappaB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-kappaB gene (RANK), and loci at 2p16 and 11p11. CONCLUSIONS: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1056/NEJMoa0801197

Full metadata record

DC FieldValue Language
dc.contributor.authorStyrkarsdottir, Unnuren
dc.contributor.authorHalldorsson, Bjarni Ven
dc.contributor.authorGretarsdottir, Solveigen
dc.contributor.authorGudbjartsson, Daniel Fen
dc.contributor.authorWalters, G Bragien
dc.contributor.authorIngvarsson, Thorvalduren
dc.contributor.authorJonsdottir, Thorbjorgen
dc.contributor.authorSaemundsdottir, Jonaen
dc.contributor.authorCenter, Jacqueline Ren
dc.contributor.authorNguyen, Tuan Ven
dc.contributor.authorBagger, Yuen
dc.contributor.authorGulcher, Jeffrey Ren
dc.contributor.authorEisman, John Aen
dc.contributor.authorChristiansen, Clausen
dc.contributor.authorSigurdsson, Gunnaren
dc.contributor.authorKong, Augustineen
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorStefansson, Karien
dc.date.accessioned2009-10-26T13:11:00Z-
dc.date.available2009-10-26T13:11:00Z-
dc.date.issued2008-05-29-
dc.date.submitted2009-10-26-
dc.identifier.citationN. Engl. J. Med. 2008, 358(22):2355-65en
dc.identifier.issn1533-4406-
dc.identifier.pmid18445777-
dc.identifier.doi10.1056/NEJMoa0801197-
dc.identifier.urihttp://hdl.handle.net/2336/84841-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. METHODS: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). RESULTS: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10(-7) to 2.0x10(-21)). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-kappaB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-kappaB gene (RANK), and loci at 2p16 and 11p11. CONCLUSIONS: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis.en
dc.language.isoenen
dc.publisherMassachusetts Medical Societyen
dc.relation.urlhttp://dx.doi.org/10.1056/NEJMoa0801197en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAustraliaen
dc.subject.meshBone Densityen
dc.subject.meshDenmarken
dc.subject.meshEstrogen Receptor alphaen
dc.subject.meshFemaleen
dc.subject.meshFractures, Boneen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshLinear Modelsen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshOsteoporosisen
dc.subject.meshOsteoprotegerinen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshQuantitative Trait Locien
dc.subject.meshRANK Liganden
dc.titleMultiple genetic loci for bone mineral density and fracturesen
dc.typeArticleen
dc.contributor.departmentdeCODE Genetics, Reykjavik, Iceland.en
dc.identifier.journalNew England journal of medicineen

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