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Nat Commun. 2016 Jan 6;7:10129. doi: 10.1038/ncomms10129.

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.

Author information

1
deCODE genetics/Amgen, 101 Reykjavik, Iceland.
2
Osteoporosis and Bone Biology, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
3
School of Medicine Sydney, University of Notre Dame Australia, Sydney, New South Wales 2010, Australia.
4
Clinical School, St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
5
Faculty of Medicine, University of New South Wales (UNSW), Sydney, New South Wales 2010, Australia.
6
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 138-736 Seoul, South Korea.
7
Centre for Health Technologies, University of Technology, Sydney, New South Wales 2010, Australia.
8
Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
9
JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
10
Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
11
Radboud University Medical Center, Radboud Institute for Health Sciences, 6500 HB Nijmegen, The Netherlands.
12
Department of Orthopedic Surgery, Akureyri Hospital, 603 Akureyri, Iceland.
13
Institution of Health Science, University of Akureyri, 603 Akureyri, Iceland.
14
Department of Chemical Pathology, and Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
15
Clinical Translation and Advanced Education, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
16
Nordic Bioscience A/S, 2730 Herlev, Denmark.
17
Department of Endocrinology and Metabolism, Landspitali, The National University Hospital of Iceland, 101 Reykjavik, Iceland.
18
Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.

Abstract

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), β=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus.

PMID:
26733130
PMCID:
PMC4729819
DOI:
10.1038/ncomms10129
[Indexed for MEDLINE]
Free PMC Article

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