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Nat Commun. 2019 May 3;10(1):2054. doi: 10.1038/s41467-019-09860-0.

GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

Author information

1
deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. unnur.styrkarsdottir@decode.is.
2
deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland.
3
Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
4
Department of Epidemiology, ErasmusMC, 3015 GD, Rotterdam, The Netherlands.
5
Department of Internal Medicine, ErasmusMC, 3015 GD, Rotterdam, the Netherlands.
6
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
7
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
8
Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
9
Faculty of Medicine, Department of Chemical Pathology and Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences,, The Chinese University of Hong Kong, Hong Kong, China.
10
CUHK Shenzhen Research Institute, Shenzhen, 518000, China.
11
Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China.
12
Faculty of Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
13
Department of Medicine, Alice Ho Miu Ling Nethersole Hospital and Tai Po Hospital, Hong Kong, China.
14
JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
15
Nordic Bioscience A/S, 2730, Herlev, Denmark.
16
Bone Biology Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
17
School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, 2010, Australia.
18
St Vincent's Clinical School, University of New South Wales, Sydney, NSW, 2010, Australia.
19
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
20
Orthopaedics, Department of Clinical Sciences Lund, Lund University, SE-22 100, Lund, Sweden.
21
Bone and Muscle Research Lab, Ton Duc Thang University, Ho Chi Minh City, 700000, Vietnam.
22
School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia.
23
Clinical Translation and Advanced Education, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
24
Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
25
Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK.
26
Institute of Translational Genomics, Helmholtz Zentrum München, 85764, München, Germany.
27
Department of Emergengy Medicine, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland.
28
Research Institute in Emergency Medicine, Landspitali, The National University Hospital of Iceland, and University of Iceland, 101, Reykjavik, Iceland.
29
Department of Medicine, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland.
30
Department of Orthopedic Surgery, Akureyri Hospital, 600, Akureyri, Iceland.
31
Institution of Health Science, University of Akureyri, 600, Akureyri, Iceland.
32
Research Service Center, Reykjavik, 201, Iceland.
33
Department of Endocrinology and Metabolism, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland.
34
Department of Immunology, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland.
35
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 107, Iceland.
36
deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. kstefans@decode.is.
37
Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. kstefans@decode.is.

Abstract

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

PMID:
31053729
PMCID:
PMC6499783
DOI:
10.1038/s41467-019-09860-0
[Indexed for MEDLINE]
Free PMC Article

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