Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro

Scott Wilson, M.R. Jones, Benjamin Mullin, Ian Dick, J.B. Richards, T.M. Pastinen, E. Grundberg, O. Ljunggren, G.L. Surdulescu, F. Dudbridge, K.S. Elliott, A.C.L. Cervino, T.D. Spector, Richard Prince

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Abstract

Previous data from our group indicate that BMD is linked to chromosome 3p14–p21. Because the filamin B (FLNB gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14–p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002–0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02–0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004–0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5′ end of the gene may reflect effects on levels of FLNB transcription efficiency.
Original languageEnglish
Pages (from-to)1989-1997
JournalJournal of Bone and Mineral Research
Volume24
Issue number12
DOIs
Publication statusPublished - 2009

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Femur Neck
Bone and Bones
Messenger RNA
Filamins
Population
Genes
Twin Studies
Computational Biology
Osteoblasts
Single Nucleotide Polymorphism
Spine
Chromosomes
Alleles
Genotype
In Vitro Techniques

Cite this

Wilson, Scott ; Jones, M.R. ; Mullin, Benjamin ; Dick, Ian ; Richards, J.B. ; Pastinen, T.M. ; Grundberg, E. ; Ljunggren, O. ; Surdulescu, G.L. ; Dudbridge, F. ; Elliott, K.S. ; Cervino, A.C.L. ; Spector, T.D. ; Prince, Richard. / Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro. In: Journal of Bone and Mineral Research. 2009 ; Vol. 24, No. 12. pp. 1989-1997.
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title = "Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro",
abstract = "Previous data from our group indicate that BMD is linked to chromosome 3p14–p21. Because the filamin B (FLNB gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14–p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002–0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02–0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004–0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5′ end of the gene may reflect effects on levels of FLNB transcription efficiency.",
author = "Scott Wilson and M.R. Jones and Benjamin Mullin and Ian Dick and J.B. Richards and T.M. Pastinen and E. Grundberg and O. Ljunggren and G.L. Surdulescu and F. Dudbridge and K.S. Elliott and A.C.L. Cervino and T.D. Spector and Richard Prince",
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Wilson, S, Jones, MR, Mullin, B, Dick, I, Richards, JB, Pastinen, TM, Grundberg, E, Ljunggren, O, Surdulescu, GL, Dudbridge, F, Elliott, KS, Cervino, ACL, Spector, TD & Prince, R 2009, 'Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro' Journal of Bone and Mineral Research, vol. 24, no. 12, pp. 1989-1997. https://doi.org/10.1359/jbmr.090530

Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro. / Wilson, Scott; Jones, M.R.; Mullin, Benjamin; Dick, Ian; Richards, J.B.; Pastinen, T.M.; Grundberg, E.; Ljunggren, O.; Surdulescu, G.L.; Dudbridge, F.; Elliott, K.S.; Cervino, A.C.L.; Spector, T.D.; Prince, Richard.

In: Journal of Bone and Mineral Research, Vol. 24, No. 12, 2009, p. 1989-1997.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common Sequence Variation in FLNB Regulates Bone Structure in Women in the General Population and FLNB mRNA Expression in Oseoblasts in Vitro

AU - Wilson, Scott

AU - Jones, M.R.

AU - Mullin, Benjamin

AU - Dick, Ian

AU - Richards, J.B.

AU - Pastinen, T.M.

AU - Grundberg, E.

AU - Ljunggren, O.

AU - Surdulescu, G.L.

AU - Dudbridge, F.

AU - Elliott, K.S.

AU - Cervino, A.C.L.

AU - Spector, T.D.

AU - Prince, Richard

PY - 2009

Y1 - 2009

N2 - Previous data from our group indicate that BMD is linked to chromosome 3p14–p21. Because the filamin B (FLNB gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14–p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002–0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02–0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004–0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5′ end of the gene may reflect effects on levels of FLNB transcription efficiency.

AB - Previous data from our group indicate that BMD is linked to chromosome 3p14–p21. Because the filamin B (FLNB gene resides in this region, is the cause of skeletal dysplasias, and was identified among the top genes in our bioinformatics analysis, we hypothesized a role for FLNB in the regulation of bone structure in the general population. Using a tag single nucleotide polymorphism (SNP) approach, a family study of 767 female sibs in which the 3p14–p21 linkage with BMD was previously shown was examined. FLNB variants showing a BMD association were tested in two additional data sets, a study of 1085 UK female twins and a population study (CAIFOS) of 1315 Australian women. Genotype-expression studies were performed in 96 human osteoblast lines to examine the variants in vitro. rs7637505, rs9822918, rs2177153, and rs2001972 showed association with femoral neck (p = 0.0002–0.02) in the family-based study. The twin study provided further support for an association between rs7637505 and femoral neck and spine BMD (p = 0.02–0.03). The CAIFOS study further suggested an association between rs2177153 and rs9822918 and femoral neck BMD (p = 0.004–0.03). Prevalent fractures were increased in carriers of the A allele of rs2177153 (p = 0.009). In vitro studies showed association between rs11130605, itself in strong LD with rs7637505, and FLNB mRNA expression. These findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at the 5′ end of the gene may reflect effects on levels of FLNB transcription efficiency.

U2 - 10.1359/jbmr.090530

DO - 10.1359/jbmr.090530

M3 - Article

VL - 24

SP - 1989

EP - 1997

JO - Journal of Bone & Mineral Research

JF - Journal of Bone & Mineral Research

SN - 0884-0431

IS - 12

ER -