SynthesisJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2010
IL21R and PTH may underlie variation of femoral neck bone mineral density as revealed by a genome-wide association study.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- P4 medicine and osteoporosis: a systematic review.Wiener klinische Wochenschrift · 2016Pooled it
- Twelve years of GWAS discoveries for osteoporosis and related traits: advances, challenges and applications.Bone research · 2021Review
- Comprehensive Genetic Analysis of 128 Candidate Genes in a Cohort With Idiopathic, Severe, or Familial Osteoporosis.Journal of the Endocrine Society · 2020Article
- Bone metabolism genes variation and response to bisphosphonate treatment in women with postmenopausal osteoporosis.PloS one · 2019Article
- A genome-wide association study meta-analysis of clinical fracture in 10,012 African American women.Bone reports · 2016Article
- The genetics of bone mass and susceptibility to bone diseases.Nature reviews. Rheumatology · 2016Review
- Genome-wide association reveals QTL for growth, bone and in vivo carcass traits as assessed by computed tomography in Scottish Blackface lambs.Genetics, selection, evolution : GSE · 2016Article
- Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing.Rheumatology international · 2016Review
- Genome-wide Survey of Runs of Homozygosity Identifies Recessive Loci for Bone Mineral Density in Caucasian and Chinese Populations.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Article
- Genetic variants in adult bone mineral density and fracture risk genes are associated with the rate of bone mineral density acquisition in adolescence.Human molecular genetics · 2015Article
- Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Article
- Genome-wide approaches for identifying genetic risk factors for osteoporosis.Genome medicine · 2013Review
- Clinical review: Genome-wide association studies of skeletal phenotypes: what we have learned and where we are headed.The Journal of clinical endocrinology and metabolism · 2012Review
- Are bone mineral density loci associated with hip osteoporotic fractures? A validation study on previously reported genome-wide association loci in a Chinese population.Genetics and molecular research : GMR · 2012Article
- Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women.PloS one · 2012Article
- VKORC1 common variation and bone mineral density in the Third National Health and Nutrition Examination Survey.PloS one · 2010Article
- Genetic epidemiology of age-related osteoporosis and its clinical applications.Nature reviews. Rheumatology · 2010Review
- Molecular genetic studies of gene identification for osteoporosis: the 2009 update.Endocrine reviews · 2010Review
- Genetics of osteoporosis: accelerating pace in gene identification and validation.Human genetics · 2010Review
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7 authors.
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Abstract
Bone mineral density (BMD) measured at the femoral neck (FN) is the most important risk phenotype for osteoporosis and has been used as a reference standard for describing osteoporosis. The specific genes influencing FN BMD remain largely unknown. To identify such genes, we first performed a genome-wide association (GWA) analysis for FN BMD in a discovery sample consisting of 983 unrelated white subjects. We then tested the top significant single-nucleotide polymorphisms (SNPs; 175 SNPs with p < 5 x 10(-4)) for replication in a family-based sample of 2557 white subjects. Combing results from these two samples, we found that two genes, parathyroid hormone (PTH) and interleukin 21 receptor (IL21R), achieved consistent association results in both the discovery and replication samples. The PTH gene SNPs, rs9630182, rs2036417, and rs7125774, achieved p values of 1.10 x 10(-4), 3.24 x 10(-4), and 3.06 x 10(-4), respectively, in the discovery sample; p values of 6.50 x 10(-4), 5.08 x 10(-3), and 5.68 x 10(-3), respectively, in the replication sample; and combined p values of 3.98 x 10(-7), 9.52 x 10(-6), and 1.05 x 10(-5), respectively, in the total sample. The IL21R gene SNPs, rs8057551, rs8061992, and rs7199138, achieved p values of 1.51 x 10(-4), 1.53 x 10(-4), and 3.88 x 10(-4), respectively, in the discovery sample; p values of 2.36 x 10(-3), 6.74 x 10(-3), and 6.41 x 10(-3), respectively, in the replication sample; and combined p values of 2.31 x 10(-6), 8.62 x 10(-6), and 1.41 x 10(-5), respectively, in the total sample. The effect size of each SNP was approximately 0.11 SD estimated in the discovery sample. PTH and IL21R both have potential biologic functions important to bone metabolism. Overall, our findings provide some new clues to the understanding of the genetic architecture of osteoporosis.
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