Search: WFRF:(Jakobsdóttir Jóhanna) >
Novel Genetic Varia...
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Nielson, Carrie M.Oregon Health & Science University
(author)
Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2
- Article/chapterEnglish2016
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:f8c025c9-929e-44a9-b7e0-a0653a09d212
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https://lup.lub.lu.se/record/f8c025c9-929e-44a9-b7e0-a0653a09d212URI
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https://doi.org/10.1002/jbmr.2913DOI
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https://gup.ub.gu.se/publication/247993URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n=15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n=21,701) and clinical vertebral fracture (n=5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF]=3%) was associated with higher vBMD (β=0.22, p=1.9×10-8) and decreased risk of radiographic vertebral fracture (odds ratio [OR]=0.75; false discovery rate [FDR] p=0.01). In 1p36.12, rs12742784 (MAF=21%) was associated with higher vBMD (β=0.09, p=1.2×10-10) and decreased risk of clinical vertebral fracture (OR=0.82; FDR p=7.4×10-4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β=0.28, FDR p=0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β=0.12, FDR p=1.7×10-3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Liu, Ching TiBoston University
(author)
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Smith, Albert V.University of Iceland
(author)
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Ackert-Bicknell, Cheryl L.University of Rochester
(author)
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Reppe, SjurUniversity of Oslo
(author)
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Jakobsdottir, JohannaIcelandic Heart Association
(author)
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Wassel, ChristinaUniversity of Vermont
(author)
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Register, Thomas C.Wake Forest University
(author)
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Oei, LingErasmus University Medical Center
(author)
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Alonso, NereaUniversity of Edinburgh
(author)
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Oei, Edwin H.Erasmus University Medical Center
(author)
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Parimi, NeetaCalifornia Pacific Medical Center
(author)
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Samelson, Elizabeth J.Harvard University
(author)
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Nalls, Mike A.National Institute on Aging, United States
(author)
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Zmuda, JosephUniversity of Pittsburgh
(author)
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Lang, ThomasUniversity of Texas Health Science Centre
(author)
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Bouxsein, MaryHarvard University
(author)
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Latourelle, JeanneBoston University
(author)
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Claussnitzer, MelinaTechnical University of Munich
(author)
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Siggeirsdottir, Kristin
(author)
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Srikanth, Priya
(author)
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Lorentzen, Erik,1974Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics(Swepub:gu)xjacer
(author)
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Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xvanli
(author)
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Langefeld, Carl
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Raffield, Laura
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Terry, GregVanderbilt University
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Cox, Amanda J.
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Allison, Matthew A.
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Criqui, Michael H.
(author)
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Bowden, Don
(author)
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Ikram, M. ArfanErasmus University Medical Center
(author)
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Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmelda
(author)
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Karlsson, Magnus K.Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Skåne University Hospital(Swepub:lu)orto-mka
(author)
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Carr, JohnVanderbilt University
(author)
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Budoff, Matthew
(author)
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Phillips, CarolineNational Institute on Aging, United States
(author)
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Cupples, L. AdrienneBoston University
(author)
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Chou, Wen ChiHelsinki University Central Hospital
(author)
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Myers, Richard H.
(author)
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Ralston, Stuart H.University of Edinburgh
(author)
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Gautvik, Kaare M.
(author)
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Cawthon, Peggy M.University of Texas Health Science Centre
(author)
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Cummings, StevenCalifornia Pacific Medical Center
(author)
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Karasik, David
(author)
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Rivadeneira, FernandoErasmus University Medical Center
(author)
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Gudnason, Vilmundur
(author)
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Orwoll, Eric S.Oregon Health & Science University
(author)
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Harris, Tamara B.National Institute on Aging, United States
(author)
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Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xohlcl
(author)
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Kiel, Douglas P.Beth Israel Deaconess Medical Center
(author)
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Hsu, Yi Hsiang
(author)
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Oregon Health & Science UniversityBoston University
(creator_code:org_t)
Related titles
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In:Journal of Bone and Mineral Research: Wiley31:12, s. 2085-20970884-0431
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In:Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research: Wiley31:12, s. 2085-20971523-4681
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- By the author/editor
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Nielson, Carrie ...
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Liu, Ching Ti
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Smith, Albert V.
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Ackert-Bicknell, ...
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Reppe, Sjur
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Jakobsdottir, Jo ...
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Wassel, Christin ...
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Register, Thomas ...
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Oei, Ling
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Alonso, Nerea
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Oei, Edwin H.
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Parimi, Neeta
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Samelson, Elizab ...
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Nalls, Mike A.
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Zmuda, Joseph
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Lang, Thomas
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Bouxsein, Mary
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Latourelle, Jean ...
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Claussnitzer, Me ...
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Siggeirsdottir, ...
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Srikanth, Priya
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Lorentzen, Erik, ...
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Vandenput, Liesb ...
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Langefeld, Carl
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Raffield, Laura
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Terry, Greg
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Cox, Amanda J.
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Allison, Matthew ...
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Criqui, Michael ...
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Bowden, Don
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Ikram, M. Arfan
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Mellström, Dan, ...
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Karlsson, Magnus ...
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Carr, John
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Budoff, Matthew
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Phillips, Caroli ...
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Cupples, L. Adri ...
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Chou, Wen Chi
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Myers, Richard H ...
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Ralston, Stuart ...
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Gautvik, Kaare M ...
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Cawthon, Peggy M ...
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Cummings, Steven
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Karasik, David
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Rivadeneira, Fer ...
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Gudnason, Vilmun ...
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Orwoll, Eric S.
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Harris, Tamara B ...
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Ohlsson, Claes, ...
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Kiel, Douglas P.
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Hsu, Yi Hsiang
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Orthopaedics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Journal of Bone ...
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Journal of bone ...
- By the university
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Lund University
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University of Gothenburg