Contribution of the LRP5 gene to normal variation in peak BMD in women

Daniel L. Koller, Shoji Ichikawa, Michelle L. Johnson, Dongbing Lai, Xiaoling Xuei, Howard Edenberg, P. Michael Conneally, Siu Hui, C. Conrad Johnston, Munro Peacock, Tatiana Foroud, Michael Econs

Research output: Contribution to journalArticle

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Abstract

The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ∼0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume20
Issue number1
DOIs
StatePublished - 2005

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Low Density Lipoprotein Receptor-Related Protein-5
Single Nucleotide Polymorphism
Genes
Spine
Hip
Femur Neck
Linkage Disequilibrium
Phenotype
Haplotypes
Population
Siblings

Keywords

  • Genetic association
  • Low-density lipoprotein receptor-related protein 5 gene
  • Peak BMD
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Surgery

Cite this

Contribution of the LRP5 gene to normal variation in peak BMD in women. / Koller, Daniel L.; Ichikawa, Shoji; Johnson, Michelle L.; Lai, Dongbing; Xuei, Xiaoling; Edenberg, Howard; Conneally, P. Michael; Hui, Siu; Johnston, C. Conrad; Peacock, Munro; Foroud, Tatiana; Econs, Michael.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 20, No. 1, 2005, p. 75-80.

Research output: Contribution to journalArticle

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abstract = "The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. Introduction: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. Materials and Methods: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. Results and Conclusions: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for ∼0.8{\%} of the variation in femoral neck BMD and 1.1{\%} of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women.",
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AU - Edenberg, Howard

AU - Conneally, P. Michael

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