Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.

BMJ : British Medical Journal
Katerina TrajanoskaGEFOS/GENOMOS consortium and the 23andMe research team

Abstract

To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standar...Continue Reading

Citations

Jan 16, 2019·BMJ : British Medical Journal·Fernando RivadeneiraJ Brent Richards
Feb 28, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·R M LucasR E Neale
May 28, 2019·Frontiers in Endocrinology·Robert D Maynard, Cheryl L Ackert-Bicknell
Jun 28, 2020·Nature Communications·Amand F SchmidtAroon D Hingorani
Sep 25, 2020·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Q ZhangH-W Deng
Jan 13, 2019·BMJ : British Medical Journal·Toshihiro Sugiyama
Jun 7, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jie ZhengJonathan H Tobias
Jun 25, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kun ZhuRichard L Prince
Nov 9, 2019·International Journal of Molecular Sciences·Kazuhiro MaedaKeishi Marumo
Oct 2, 2020·Communications Biology·Katerina TrajanoskaFernando Rivadeneira
Sep 12, 2018·Current Osteoporosis Reports·Katerina Trajanoska, Fernando Rivadeneira
Feb 13, 2019·European Journal of Epidemiology·John P A Ioannidis
Feb 5, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Joyce Bj van MeursJose A Riancho
May 6, 2019·Nature Communications·Unnur StyrkarsdottirKari Stefansson
Apr 25, 2020·Frontiers in Endocrinology·Yentl HuybrechtsWim Van Hul
Mar 13, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jie ZhengDavid M Evans
Sep 9, 2020·Current Osteoporosis Reports·M A ChristouD Karasik
Jun 25, 2019·Frontiers in Endocrinology·Fjorda KoromaniLing Oei
Jan 26, 2020·Calcified Tissue International·Ken-Ichiro TanakaToshitsugu Sugimoto
Mar 20, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yi-Hsiang HsuDavid Karasik
Apr 12, 2019·Frontiers in Endocrinology·Nicholas G NorwitzKathryn E Ackerman
Dec 12, 2019·Frontiers in Endocrinology·Jie ZhengJonathan H Tobias
Dec 4, 2019·Nature Reviews. Endocrinology·Tie-Lin YangHong-Wen Deng
Jun 20, 2020·ELife·Marie PereiraJacques Behmoaras
Aug 23, 2020·The Journal of Clinical Endocrinology and Metabolism·Yong LiuHong-Wen Deng
Aug 11, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Douglas P KielNoël Burtt
Sep 22, 2019·The Journal of Steroid Biochemistry and Molecular Biology·Rolf JordeGuri Grimnes
Jul 1, 2020·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Zhenyu ZhongPeizeng Yang

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BETA
genotyping

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METAL
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