Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women

Shoji Ichikawa, Daniel L. Koller, Leah R. Curry, Dongbing Lai, Xiaoling Xuei, Elizabeth W. Pugh, Ya Yu Tsai, Kimberly F. Doheny, Howard Edenberg, Siu Hui, Tatiana Foroud, Munro Peacock, Michael Econs

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10-6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10-5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10-7) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.

Original languageEnglish
Pages (from-to)1680-1688
Number of pages9
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume23
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Linkage Disequilibrium
Chromosomes
Single Nucleotide Polymorphism
Genes
Spine
Osteoporotic Fractures
Femur Neck
Osteoporosis

Keywords

  • BMD
  • Genetic association
  • Linkage disequilibrium block
  • Osteoporosis
  • SNP

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women. / Ichikawa, Shoji; Koller, Daniel L.; Curry, Leah R.; Lai, Dongbing; Xuei, Xiaoling; Pugh, Elizabeth W.; Tsai, Ya Yu; Doheny, Kimberly F.; Edenberg, Howard; Hui, Siu; Foroud, Tatiana; Peacock, Munro; Econs, Michael.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 23, No. 10, 10.2008, p. 1680-1688.

Research output: Contribution to journalArticle

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abstract = "Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10-6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10-5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10-7) accounted for >2.5{\%} of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.",
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AU - Xuei, Xiaoling

AU - Pugh, Elizabeth W.

AU - Tsai, Ya Yu

AU - Doheny, Kimberly F.

AU - Edenberg, Howard

AU - Hui, Siu

AU - Foroud, Tatiana

AU - Peacock, Munro

AU - Econs, Michael

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N2 - Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10-6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10-5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10-7) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.

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