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FältnamnIndikatorerMetadata
00009650naa a2201321 4500
001oai:gup.ub.gu.se/75078
003SwePub
008240528s2008 | |||||||||||000 ||eng|
009oai:DiVA.org:umu-9385
009oai:lup.lub.lu.se:cbe81e42-de1f-495e-847c-e590b8c28435
009oai:DiVA.org:uu-110490
0247 a https://gup.ub.gu.se/publication/750782 URI
0247 a https://doi.org/10.1001/jama.299.11.12772 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-93852 URI
0247 a https://lup.lub.lu.se/record/11860322 URI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1104902 URI
040 a (SwePub)gud (SwePub)umud (SwePub)lud (SwePub)uu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a van Meurs, Joyce Bu Erasmus University Medical Center4 aut
2451 0a Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
264 1a Chicago :b American Medical Association (AMA),c 2008
520 a CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Ortopedi0 (SwePub)302112 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Orthopaedics0 (SwePub)302112 hsv//eng
653 a Bone Density
653 a genetics
653 a Femur Neck
653 a Fractures
653 a Bone
653 a epidemiology
653 a genetics
653 a Genotype
653 a Humans
653 a LDL-Receptor Related Proteins
653 a genetics
653 a Lumbar Vertebrae
653 a Osteoporosis
653 a epidemiology
653 a genetics
653 a Phenotype
653 a Polymorphism
653 a Single Nucleotide
653 a Prospective Studies
653 a Risk Factors
653 a Spinal Fractures
653 a epidemiology
653 a genetics
653 a Bone Density/*genetics
653 a Fractures, Bone
653 a Low Density Lipoprotein Receptor-Related Protein-5
653 a Low Density Lipoprotein Receptor-Related Protein-6
653 a Polymorphism, Single Nucleotide
653 a Journal Article
653 a Research Support, N.I.H., Extramural
653 a Research Support, Non-U.S. Gov't
653 a MEDICINE
7001 a Trikalinos, Thomas A4 aut
7001 a Ralston, Stuart H4 aut
7001 a Balcells, Susana4 aut
7001 a Brandi, Maria Luisa4 aut
7001 a Brixen, Kim4 aut
7001 a Kiel, Douglas P4 aut
7001 a Langdahl, Bente L4 aut
7001 a Lips, Paul4 aut
7001 a Ljunggren, Östenu Uppsala universitet,Institutionen för medicinska vetenskaper,Metabolic Bone Disease4 aut0 (Swepub:uu)osteljun
7001 a Lorenc, Roman4 aut
7001 a Obermayer-Pietsch, Barbara4 aut
7001 a Ohlsson, Claes,d 1965u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine4 aut0 (Swepub:gu)xohlcl
7001 a Pettersson, Ulrikau Umeå universitet,Klinisk farmakologi4 aut0 (Swepub:umu)ulpe0007
7001 a Reid, David M4 aut
7001 a Rousseau, Francois4 aut
7001 a Scollen, Serena4 aut
7001 a Van Hul, Wim4 aut
7001 a Agueda, Lidia4 aut
7001 a Akesson, Kristinau Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups4 aut0 (Swepub:lu)orto-kak
7001 a Benevolenskaya, Lidia I4 aut
7001 a Ferrari, Serge L4 aut
7001 a Hallmans, Göranu Umeå universitet,Näringsforskning4 aut0 (Swepub:umu)goha0001
7001 a Hofman, Albert4 aut
7001 a Husted, Lise Bjerre4 aut
7001 a Kruk, Marcin4 aut
7001 a Kaptoge, Stephen4 aut
7001 a Karasik, David4 aut
7001 a Karlsson, Magnus Ku Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine4 aut0 (Swepub:lu)orto-mka
7001 a Lorentzon, Mattias,d 1970u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine4 aut0 (Swepub:gu)xlomat
7001 a Masi, Laura4 aut
7001 a McGuigan, Fiona E Au Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups4 aut0 (Swepub:lu)med-fam
7001 a Mellström, Dan,d 1945u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, School of Public Health and Community Medicine4 aut0 (Swepub:gu)xmelda
7001 a Mosekilde, Leif4 aut
7001 a Nogues, Xavier4 aut
7001 a Pols, Huibert A P4 aut
7001 a Reeve, Jonathan4 aut
7001 a Renner, Wilfried4 aut
7001 a Rivadeneira, Fernando4 aut
7001 a van Schoor, Natasja M4 aut
7001 a Weber, Kurt4 aut
7001 a Ioannidis, John P A4 aut
7001 a Uitterlinden, André G4 aut
7102 a Erasmus University Medical Centerb Institutionen för medicinska vetenskaper4 org
7730 t JAMA : the journal of the American Medical Associationd Chicago : American Medical Association (AMA)g 299:11, s. 1277-90q 299:11<1277-90x 1538-3598x 0098-7484
7730 t JAMAd Chicago : American Medical Association (AMA)g 299:11, s. 1277-90q 299:11<1277-90x 0098-7484
8564 u https://jamanetwork.com/journals/jama/articlepdf/181639/joc80014_1277_1290.pdf
8564 u http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=18349089&dopt=Citation
8564 u http://jama.ama-assn.org/cgi/content/full/299/11/1277y FULLTEXT
8564 u http://dx.doi.org/10.1001/jama.299.11.1277y FULLTEXT
8564 8u https://gup.ub.gu.se/publication/75078
8564 8u https://doi.org/10.1001/jama.299.11.1277
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-9385
8564 8u https://lup.lub.lu.se/record/1186032
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110490

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