Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density

Hong Wen Deng, Hui Shen, Fu Hua Xu, Hong Yi Deng, Theresa Conway, Hai Tao Zhang, Robert R. Recker

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Bone mineral density (BMD) is a major determinant of osteoporotic fractures (OFs). The heritability of BMD ranges from 50% to 90% in human populations. Extensive molecular genetic analyses have been performed through traditional linkage or association approaches to test and identify genes or genomic regions underlying BMD variation. The results, particularly those concerning the vitamin D receptor (VDR) gene, have been inconsistent and controversial. In this study, we simultaneously test linkage and/or association of the genes for VDR, osteocalcin (also known as bone Gla protein [BGP]), and parathyroid hormone (PTH) with BMD in 630 subjects from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with an extreme BMD value at the hip or spine (Z score ≤ -1.28). For the raw BMD values, adjusting for significant covariate effects of age, sex, and weight, we performed tests for linkage alone, association alone, and then both linkage and association. For the spine BMD, at the two markers (ApaI and FokI) inside the VDR gene we found evidence for linkage (p <0.05) and for both linkage and association by the transmission disequilibrium test (TDT; p <0.05); association was detected (p <0.07) with regular statistical testing by analyses of variance (ANOVA). In addition, significant results were found for association alone (p <0.05), linkage alone (p = 0.0005), and for linkage and association (p = 0.0019) for the intragenic marker HindIII of the BGP gene for the hip BMD. Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation. However, our data do not support the PTH gene as a QTL underlying hip or spine BMD variation. This is the first study in the broad field of bone genetics that tests candidate genes as QTLs for BMD by testing simultaneously for association alone, for linkage alone, and for association and linkage (via the TDT).

Original languageEnglish
Pages (from-to)678-686
Number of pages9
JournalJournal of Bone and Mineral Research
Volume17
Issue number4
StatePublished - 2002

Fingerprint

Calcitriol Receptors
Osteocalcin
Parathyroid Hormone
Bone Density
Genes
Quantitative Trait Loci
Spine
Pelvic Bones
Pedigree
Hip
Osteoporotic Fractures
Molecular Biology
Analysis of Variance

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. / Deng, Hong Wen; Shen, Hui; Xu, Fu Hua; Deng, Hong Yi; Conway, Theresa; Zhang, Hai Tao; Recker, Robert R.

In: Journal of Bone and Mineral Research, Vol. 17, No. 4, 2002, p. 678-686.

Research output: Contribution to journalArticle

Deng, Hong Wen ; Shen, Hui ; Xu, Fu Hua ; Deng, Hong Yi ; Conway, Theresa ; Zhang, Hai Tao ; Recker, Robert R. / Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. In: Journal of Bone and Mineral Research. 2002 ; Vol. 17, No. 4. pp. 678-686.
@article{b492dd8c8db744d3a973fda5d94cea76,
title = "Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density",
abstract = "Bone mineral density (BMD) is a major determinant of osteoporotic fractures (OFs). The heritability of BMD ranges from 50{\%} to 90{\%} in human populations. Extensive molecular genetic analyses have been performed through traditional linkage or association approaches to test and identify genes or genomic regions underlying BMD variation. The results, particularly those concerning the vitamin D receptor (VDR) gene, have been inconsistent and controversial. In this study, we simultaneously test linkage and/or association of the genes for VDR, osteocalcin (also known as bone Gla protein [BGP]), and parathyroid hormone (PTH) with BMD in 630 subjects from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with an extreme BMD value at the hip or spine (Z score ≤ -1.28). For the raw BMD values, adjusting for significant covariate effects of age, sex, and weight, we performed tests for linkage alone, association alone, and then both linkage and association. For the spine BMD, at the two markers (ApaI and FokI) inside the VDR gene we found evidence for linkage (p <0.05) and for both linkage and association by the transmission disequilibrium test (TDT; p <0.05); association was detected (p <0.07) with regular statistical testing by analyses of variance (ANOVA). In addition, significant results were found for association alone (p <0.05), linkage alone (p = 0.0005), and for linkage and association (p = 0.0019) for the intragenic marker HindIII of the BGP gene for the hip BMD. Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation. However, our data do not support the PTH gene as a QTL underlying hip or spine BMD variation. This is the first study in the broad field of bone genetics that tests candidate genes as QTLs for BMD by testing simultaneously for association alone, for linkage alone, and for association and linkage (via the TDT).",
author = "Deng, {Hong Wen} and Hui Shen and Xu, {Fu Hua} and Deng, {Hong Yi} and Theresa Conway and Zhang, {Hai Tao} and Recker, {Robert R.}",
year = "2002",
language = "English",
volume = "17",
pages = "678--686",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density

AU - Deng, Hong Wen

AU - Shen, Hui

AU - Xu, Fu Hua

AU - Deng, Hong Yi

AU - Conway, Theresa

AU - Zhang, Hai Tao

AU - Recker, Robert R.

PY - 2002

Y1 - 2002

N2 - Bone mineral density (BMD) is a major determinant of osteoporotic fractures (OFs). The heritability of BMD ranges from 50% to 90% in human populations. Extensive molecular genetic analyses have been performed through traditional linkage or association approaches to test and identify genes or genomic regions underlying BMD variation. The results, particularly those concerning the vitamin D receptor (VDR) gene, have been inconsistent and controversial. In this study, we simultaneously test linkage and/or association of the genes for VDR, osteocalcin (also known as bone Gla protein [BGP]), and parathyroid hormone (PTH) with BMD in 630 subjects from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with an extreme BMD value at the hip or spine (Z score ≤ -1.28). For the raw BMD values, adjusting for significant covariate effects of age, sex, and weight, we performed tests for linkage alone, association alone, and then both linkage and association. For the spine BMD, at the two markers (ApaI and FokI) inside the VDR gene we found evidence for linkage (p <0.05) and for both linkage and association by the transmission disequilibrium test (TDT; p <0.05); association was detected (p <0.07) with regular statistical testing by analyses of variance (ANOVA). In addition, significant results were found for association alone (p <0.05), linkage alone (p = 0.0005), and for linkage and association (p = 0.0019) for the intragenic marker HindIII of the BGP gene for the hip BMD. Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation. However, our data do not support the PTH gene as a QTL underlying hip or spine BMD variation. This is the first study in the broad field of bone genetics that tests candidate genes as QTLs for BMD by testing simultaneously for association alone, for linkage alone, and for association and linkage (via the TDT).

AB - Bone mineral density (BMD) is a major determinant of osteoporotic fractures (OFs). The heritability of BMD ranges from 50% to 90% in human populations. Extensive molecular genetic analyses have been performed through traditional linkage or association approaches to test and identify genes or genomic regions underlying BMD variation. The results, particularly those concerning the vitamin D receptor (VDR) gene, have been inconsistent and controversial. In this study, we simultaneously test linkage and/or association of the genes for VDR, osteocalcin (also known as bone Gla protein [BGP]), and parathyroid hormone (PTH) with BMD in 630 subjects from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with an extreme BMD value at the hip or spine (Z score ≤ -1.28). For the raw BMD values, adjusting for significant covariate effects of age, sex, and weight, we performed tests for linkage alone, association alone, and then both linkage and association. For the spine BMD, at the two markers (ApaI and FokI) inside the VDR gene we found evidence for linkage (p <0.05) and for both linkage and association by the transmission disequilibrium test (TDT; p <0.05); association was detected (p <0.07) with regular statistical testing by analyses of variance (ANOVA). In addition, significant results were found for association alone (p <0.05), linkage alone (p = 0.0005), and for linkage and association (p = 0.0019) for the intragenic marker HindIII of the BGP gene for the hip BMD. Through testing for association, linkage, and linkage and association simultaneously, our data support the VDR gene as a quantitative trait locus (QTL) underlying spine BMD variation and the BGP gene as a QTL underlying hip BMD variation. However, our data do not support the PTH gene as a QTL underlying hip or spine BMD variation. This is the first study in the broad field of bone genetics that tests candidate genes as QTLs for BMD by testing simultaneously for association alone, for linkage alone, and for association and linkage (via the TDT).

UR - http://www.scopus.com/inward/record.url?scp=0036126883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036126883&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 678

EP - 686

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 4

ER -