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

https://arctichealth.org/en/permalink/ahliterature273497
Source
Nat Commun. 2016;7:10129
Publication Type
Article
Date
2016
Author
Unnur Styrkarsdottir
Gudmar Thorleifsson
Sigurjon A Gudjonsson
Asgeir Sigurdsson
Jacqueline R Center
Seung Hun Lee
Tuan V Nguyen
Timothy C Y Kwok
Jenny S W Lee
Suzanne C Ho
Jean Woo
Ping-C Leung
Beom-Jun Kim
Thorunn Rafnar
Lambertus A Kiemeney
Thorvaldur Ingvarsson
Jung-Min Koh
Nelson L S Tang
John A Eisman
Claus Christiansen
Gunnar Sigurdsson
Unnur Thorsteinsdottir
Kari Stefansson
Source
Nat Commun. 2016;7:10129
Date
2016
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Bone Density - genetics
Female
Fractures, Spontaneous - genetics - pathology
Gene Expression Regulation - physiology
Genetic Variation
Genome-Wide Association Study
Genotype
Humans
Iceland
Male
Middle Aged
Osteoporosis - complications
Receptors, Cell Surface - genetics - metabolism
Spine - physiology
Thrombospondins - genetics - metabolism
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), ß=-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), ß=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.
Notes
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PubMed ID
26733130 View in PubMed
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Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland.

https://arctichealth.org/en/permalink/ahliterature277507
Source
J Bone Miner Res. 2016 Jan;31(1):173-9
Publication Type
Article
Date
Jan-2016
Author
Unnur Styrkarsdottir
Gudmar Thorleifsson
Berglind Eiriksdottir
Sigurjon A Gudjonsson
Thorvaldur Ingvarsson
Jacqueline R Center
Tuan V Nguyen
John A Eisman
Claus Christiansen
Unnur Thorsteinsdottir
Gunnar Sigurdsson
Kari Stefansson
Source
J Bone Miner Res. 2016 Jan;31(1):173-9
Date
Jan-2016
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Bone Density - genetics
Collagen Type I - genetics
Female
Fractures, Bone - epidemiology - genetics
Humans
INDEL Mutation
Iceland - epidemiology
Male
Middle Aged
Polymorphism, Single Nucleotide
Abstract
We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures of osteoporosis in Icelanders. Mutations in COL1A2 are known to cause the autosomal dominant disorder osteogenesis imperfecta. Both variants associate with low BMD and with osteoporotic fractures. p.Gly496Ala (frequency of 0.105%) shows the strongest association with low BMD at the spine (p?=?1.8?×?10(-7) , odds ratio [OR]?=?4.61 [95% confidence interval (CI) 2.59, 8.18]), whereas p.Gly703Ser (frequency of 0.050%) is most strongly associated with low BMD at the hip (p?=?1.9?×?10(-8) , OR?=?9.34 [95% CI 4.28, 20.3]). Association with fractures was p?=?2.2?×?10(-5) , OR?=?3.75 (95% CI 2.03, 6.93) and p?=?0.0023, OR?=?4.32 (95% CI 1.69, 11.1), respectively. The carriers of these variants do not have signs of osteogenesis imperfecta other than low BMD, demonstrating that similar mutations in COL1A2 can affect skeletal phenotypes in more than one way.
PubMed ID
26235824 View in PubMed
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