Multiple genetic loci for bone mineral density and fractures
Background: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. Methods: We performed a quantitative trait analysis of data from 5861...
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ftunivtsydney:oai:opus.lib.uts.edu.au:10453/28797 2023-05-15T16:52:48+02:00 Multiple genetic loci for bone mineral density and fractures Styrkarsdottir, U Halldorsson, BV Gretarsdottir, S Gudbjartsson, DF Walters, GB Ingvarsson, T Jonsdottir, T Saemundsdottir, J Center, JR Nguyen, TV Bagger, Y Gulcher, JR Eisman, JA Christiansen, C Sigurdsson, G Kong, A Thorsteinsdottir, U Stefansson, K 2008-05-29 application/pdf http://hdl.handle.net/10453/28797 unknown New England Journal of Medicine 10.1056/NEJMoa0801197 New England Journal of Medicine, 2008, 358 (22), pp. 2355 - 2365 0028-4793 http://hdl.handle.net/10453/28797 General & Internal Medicine Humans Osteoporosis Estrogen Receptor alpha Linear Models Bone Density Genotype Polymorphism Single Nucleotide Quantitative Trait Loci Adolescent Adult Aged 80 and over Middle Aged Australia Iceland Denmark Female Male Fractures Bone RANK Ligand Osteoprotegerin Journal Article 2008 ftunivtsydney 2022-03-13T13:59:46Z Background: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. Methods: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). Results: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10-7 to 2.0x10-21). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-κB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-κB gene (RANK), and loci at 2p16 and 11p11. Conclusions: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis. Copyright © 2008 Massachusetts Medical Society. Article in Journal/Newspaper Iceland University of Technology Sydney: OPUS - Open Publications of UTS Scholars |
institution |
Open Polar |
collection |
University of Technology Sydney: OPUS - Open Publications of UTS Scholars |
op_collection_id |
ftunivtsydney |
language |
unknown |
topic |
General & Internal Medicine Humans Osteoporosis Estrogen Receptor alpha Linear Models Bone Density Genotype Polymorphism Single Nucleotide Quantitative Trait Loci Adolescent Adult Aged 80 and over Middle Aged Australia Iceland Denmark Female Male Fractures Bone RANK Ligand Osteoprotegerin |
spellingShingle |
General & Internal Medicine Humans Osteoporosis Estrogen Receptor alpha Linear Models Bone Density Genotype Polymorphism Single Nucleotide Quantitative Trait Loci Adolescent Adult Aged 80 and over Middle Aged Australia Iceland Denmark Female Male Fractures Bone RANK Ligand Osteoprotegerin Styrkarsdottir, U Halldorsson, BV Gretarsdottir, S Gudbjartsson, DF Walters, GB Ingvarsson, T Jonsdottir, T Saemundsdottir, J Center, JR Nguyen, TV Bagger, Y Gulcher, JR Eisman, JA Christiansen, C Sigurdsson, G Kong, A Thorsteinsdottir, U Stefansson, K Multiple genetic loci for bone mineral density and fractures |
topic_facet |
General & Internal Medicine Humans Osteoporosis Estrogen Receptor alpha Linear Models Bone Density Genotype Polymorphism Single Nucleotide Quantitative Trait Loci Adolescent Adult Aged 80 and over Middle Aged Australia Iceland Denmark Female Male Fractures Bone RANK Ligand Osteoprotegerin |
description |
Background: Bone mineral density influences the risk of osteoporosis later in life and is useful in the evaluation of the risk of fracture. We aimed to identify sequence variants associated with bone mineral density and fracture. Methods: We performed a quantitative trait analysis of data from 5861 Icelandic subjects (the discovery set), testing for an association between 301,019 single-nucleotide polymorphisms (SNPs) and bone mineral density of the hip and lumbar spine. We then tested for an association between 74 SNPs (most of which were implicated in the discovery set) at 32 loci in replication sets of Icelandic, Danish, and Australian subjects (4165, 2269, and 1491 subjects, respectively). Results: Sequence variants in five genomic regions were significantly associated with bone mineral density in the discovery set and were confirmed in the replication sets (combined P values, 1.2x10-7 to 2.0x10-21). Three regions are close to or within genes previously shown to be important to the biologic characteristics of bone: the receptor activator of nuclear factor-κB ligand gene (RANKL) (chromosomal location, 13q14), the osteoprotegerin gene (OPG) (8q24), and the estrogen receptor 1 gene (ESR1) (6q25). The two other regions are close to the zinc finger and BTB domain containing 40 gene (ZBTB40) (1p36) and the major histocompatibility complex region (6p21). The 1p36, 8q24, and 6p21 loci were also associated with osteoporotic fractures, as were loci at 18q21, close to the receptor activator of the nuclear factor-κB gene (RANK), and loci at 2p16 and 11p11. Conclusions: We have discovered common sequence variants that are consistently associated with bone mineral density and with low-trauma fractures in three populations of European descent. Although these variants alone are not clinically useful in the prediction of risk to the individual person, they provide insight into the biochemical pathways underlying osteoporosis. Copyright © 2008 Massachusetts Medical Society. |
format |
Article in Journal/Newspaper |
author |
Styrkarsdottir, U Halldorsson, BV Gretarsdottir, S Gudbjartsson, DF Walters, GB Ingvarsson, T Jonsdottir, T Saemundsdottir, J Center, JR Nguyen, TV Bagger, Y Gulcher, JR Eisman, JA Christiansen, C Sigurdsson, G Kong, A Thorsteinsdottir, U Stefansson, K |
author_facet |
Styrkarsdottir, U Halldorsson, BV Gretarsdottir, S Gudbjartsson, DF Walters, GB Ingvarsson, T Jonsdottir, T Saemundsdottir, J Center, JR Nguyen, TV Bagger, Y Gulcher, JR Eisman, JA Christiansen, C Sigurdsson, G Kong, A Thorsteinsdottir, U Stefansson, K |
author_sort |
Styrkarsdottir, U |
title |
Multiple genetic loci for bone mineral density and fractures |
title_short |
Multiple genetic loci for bone mineral density and fractures |
title_full |
Multiple genetic loci for bone mineral density and fractures |
title_fullStr |
Multiple genetic loci for bone mineral density and fractures |
title_full_unstemmed |
Multiple genetic loci for bone mineral density and fractures |
title_sort |
multiple genetic loci for bone mineral density and fractures |
publishDate |
2008 |
url |
http://hdl.handle.net/10453/28797 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
New England Journal of Medicine 10.1056/NEJMoa0801197 New England Journal of Medicine, 2008, 358 (22), pp. 2355 - 2365 0028-4793 http://hdl.handle.net/10453/28797 |
_version_ |
1766043209265315840 |