Multiple genetic loci for bone mineral density and fractures. Export

@article{citeulike:2846117, abstract = {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-kappaB 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-kappaB 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.}, author = {Styrkarsdottir, Unnur and Halldorsson, Bjarni V. and Gretarsdottir, Solveig and Gudbjartsson, Daniel F. and Walters, G. Bragi and Ingvarsson, Thorvaldur and Jonsdottir, Thorbjorg and Saemundsdottir, Jona and Center, Jacqueline R. and Nguyen, Tuan V. and Bagger, Yu and Gulcher, Jeffrey R. and Eisman, John A. and Christiansen, Claus and Sigurdsson, Gunnar and Kong, Augustine and Thorsteinsdottir, Unnur and Stefansson, Kari}, citeulike-article-id = {2846117}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa0801197}, citeulike-linkout-1 = {http://content.nejm.org/content/358/22/2355.abstract}, citeulike-linkout-2 = {http://content.nejm.org/content/358/22/2355.full.pdf}, citeulike-linkout-3 = {http://content.nejm.org/cgi/content/abstract/358/22/2355}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/18445777}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=18445777}, day = {29}, doi = {10.1056/NEJMoa0801197}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {bmd, bone, gwas}, month = {May}, number = {22}, pages = {2355--2365}, posted-at = {2009-11-02 16:06:45}, priority = {2}, title = {Multiple genetic loci for bone mineral density and fractures.}, url = {http://dx.doi.org/10.1056/NEJMoa0801197}, volume = {358}, year = {2008} }

TY - JOUR ID - citeulike:2846117 L3 - citeulike-article-id:2846117 N2 - 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-kappaB 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-kappaB 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. IS - 22 JF - The New England journal of medicine SN - 1533-4406 EP - 2365 TI - Multiple genetic loci for bone mineral density and fractures. VL - 358 SP - 2355 KW - bmd KW - bone KW - gwas AU - Styrkarsdottir, Unnur AU - Halldorsson, Bjarni AU - Gretarsdottir, Solveig AU - Gudbjartsson, Daniel AU - Walters, Bragi AU - Ingvarsson, Thorvaldur AU - Jonsdottir, Thorbjorg AU - Saemundsdottir, Jona AU - Center, Jacqueline AU - Nguyen, Tuan AU - Bagger, Yu AU - Gulcher, Jeffrey AU - Eisman, John AU - Christiansen, Claus AU - Sigurdsson, Gunnar AU - Kong, Augustine AU - Thorsteinsdottir, Unnur AU - Stefansson, Kari PY - 2008/05/29/ UR - http://dx.doi.org/10.1056/NEJMoa0801197 ER -