Copy number variation of the APC gene is associated with regulation of bone mineral density

S. Chew, Z. Dastani, S.J. Brown, Joshua Lewis, F. Dudbridge, N. Soranzo, G.L. Surdulescu, J.B. Richards, T.D. Spector, Scott Wilson

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Genetic studies of osteoporosis have commonly examined SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called copy number variations (CNVs), also comprise a large amount of the genetic variability between individuals. Previously, SNPs in the APC gene have been strongly associated with femoral neck and lumbar spine volumetric bone mineral density in older men. In addition, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean bone mineral density than age- and sex-matched controls suggesting the importance of this gene in regulating bone mineral density. We examined CNV within the APC gene region to test for association with bone mineral density.Methods: DNA was extracted from venous blood, genotyped using the Human Hap610 arrays and CNV determined from the fluorescence intensity data in 2070 Caucasian men and women aged 47.0 ± 13.0 (mean ± SD) years, to assess the effects of the CNV on bone mineral density at the forearm, spine and total hip sites.Results: Data for covariate adjusted bone mineral density from subjects grouped by APC CNV genotype showed significant difference (P = 0.02–0.002). Subjects with a single copy loss of APC had a 7.95%, 13.10% and 13.36% increase in bone mineral density at the forearm, spine and total hip sites respectively, compared to subjects with two copies of the APC gene.Conclusions: These data support previous findings of APC regulating bone mineral density and demonstrate that a novel CNV of the APC gene is significantly associated with bone mineral density in Caucasian men and women.
Original languageEnglish
Pages (from-to)939-943
JournalBone
Volume51
Issue number5
Early online date1 Aug 2012
DOIs
Publication statusPublished - Nov 2012

Fingerprint

APC Genes
Bone Density
Spine
Forearm
Single Nucleotide Polymorphism
Hip
Adenomatous Polyposis Coli
DNA
Femur Neck
Genes
Osteoporosis
Fluorescence
Genotype
Genome

Cite this

Chew, S. ; Dastani, Z. ; Brown, S.J. ; Lewis, Joshua ; Dudbridge, F. ; Soranzo, N. ; Surdulescu, G.L. ; Richards, J.B. ; Spector, T.D. ; Wilson, Scott. / Copy number variation of the APC gene is associated with regulation of bone mineral density. In: Bone. 2012 ; Vol. 51, No. 5. pp. 939-943.
@article{83b4a6437a2c432a990dc18b02b5e4fb,
title = "Copy number variation of the APC gene is associated with regulation of bone mineral density",
abstract = "Introduction: Genetic studies of osteoporosis have commonly examined SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called copy number variations (CNVs), also comprise a large amount of the genetic variability between individuals. Previously, SNPs in the APC gene have been strongly associated with femoral neck and lumbar spine volumetric bone mineral density in older men. In addition, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean bone mineral density than age- and sex-matched controls suggesting the importance of this gene in regulating bone mineral density. We examined CNV within the APC gene region to test for association with bone mineral density.Methods: DNA was extracted from venous blood, genotyped using the Human Hap610 arrays and CNV determined from the fluorescence intensity data in 2070 Caucasian men and women aged 47.0 ± 13.0 (mean ± SD) years, to assess the effects of the CNV on bone mineral density at the forearm, spine and total hip sites.Results: Data for covariate adjusted bone mineral density from subjects grouped by APC CNV genotype showed significant difference (P = 0.02–0.002). Subjects with a single copy loss of APC had a 7.95{\%}, 13.10{\%} and 13.36{\%} increase in bone mineral density at the forearm, spine and total hip sites respectively, compared to subjects with two copies of the APC gene.Conclusions: These data support previous findings of APC regulating bone mineral density and demonstrate that a novel CNV of the APC gene is significantly associated with bone mineral density in Caucasian men and women.",
author = "S. Chew and Z. Dastani and S.J. Brown and Joshua Lewis and F. Dudbridge and N. Soranzo and G.L. Surdulescu and J.B. Richards and T.D. Spector and Scott Wilson",
year = "2012",
month = "11",
doi = "10.1016/j.bone.2012.07.022",
language = "English",
volume = "51",
pages = "939--943",
journal = "Bone",
issn = "8756-3282",
publisher = "Academic Press",
number = "5",

}

Chew, S, Dastani, Z, Brown, SJ, Lewis, J, Dudbridge, F, Soranzo, N, Surdulescu, GL, Richards, JB, Spector, TD & Wilson, S 2012, 'Copy number variation of the APC gene is associated with regulation of bone mineral density' Bone, vol. 51, no. 5, pp. 939-943. https://doi.org/10.1016/j.bone.2012.07.022

Copy number variation of the APC gene is associated with regulation of bone mineral density. / Chew, S.; Dastani, Z.; Brown, S.J.; Lewis, Joshua; Dudbridge, F.; Soranzo, N.; Surdulescu, G.L.; Richards, J.B.; Spector, T.D.; Wilson, Scott.

In: Bone, Vol. 51, No. 5, 11.2012, p. 939-943.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Copy number variation of the APC gene is associated with regulation of bone mineral density

AU - Chew, S.

AU - Dastani, Z.

AU - Brown, S.J.

AU - Lewis, Joshua

AU - Dudbridge, F.

AU - Soranzo, N.

AU - Surdulescu, G.L.

AU - Richards, J.B.

AU - Spector, T.D.

AU - Wilson, Scott

PY - 2012/11

Y1 - 2012/11

N2 - Introduction: Genetic studies of osteoporosis have commonly examined SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called copy number variations (CNVs), also comprise a large amount of the genetic variability between individuals. Previously, SNPs in the APC gene have been strongly associated with femoral neck and lumbar spine volumetric bone mineral density in older men. In addition, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean bone mineral density than age- and sex-matched controls suggesting the importance of this gene in regulating bone mineral density. We examined CNV within the APC gene region to test for association with bone mineral density.Methods: DNA was extracted from venous blood, genotyped using the Human Hap610 arrays and CNV determined from the fluorescence intensity data in 2070 Caucasian men and women aged 47.0 ± 13.0 (mean ± SD) years, to assess the effects of the CNV on bone mineral density at the forearm, spine and total hip sites.Results: Data for covariate adjusted bone mineral density from subjects grouped by APC CNV genotype showed significant difference (P = 0.02–0.002). Subjects with a single copy loss of APC had a 7.95%, 13.10% and 13.36% increase in bone mineral density at the forearm, spine and total hip sites respectively, compared to subjects with two copies of the APC gene.Conclusions: These data support previous findings of APC regulating bone mineral density and demonstrate that a novel CNV of the APC gene is significantly associated with bone mineral density in Caucasian men and women.

AB - Introduction: Genetic studies of osteoporosis have commonly examined SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called copy number variations (CNVs), also comprise a large amount of the genetic variability between individuals. Previously, SNPs in the APC gene have been strongly associated with femoral neck and lumbar spine volumetric bone mineral density in older men. In addition, familial adenomatous polyposis patients carrying heterozygous mutations in the APC gene have been shown to have significantly higher mean bone mineral density than age- and sex-matched controls suggesting the importance of this gene in regulating bone mineral density. We examined CNV within the APC gene region to test for association with bone mineral density.Methods: DNA was extracted from venous blood, genotyped using the Human Hap610 arrays and CNV determined from the fluorescence intensity data in 2070 Caucasian men and women aged 47.0 ± 13.0 (mean ± SD) years, to assess the effects of the CNV on bone mineral density at the forearm, spine and total hip sites.Results: Data for covariate adjusted bone mineral density from subjects grouped by APC CNV genotype showed significant difference (P = 0.02–0.002). Subjects with a single copy loss of APC had a 7.95%, 13.10% and 13.36% increase in bone mineral density at the forearm, spine and total hip sites respectively, compared to subjects with two copies of the APC gene.Conclusions: These data support previous findings of APC regulating bone mineral density and demonstrate that a novel CNV of the APC gene is significantly associated with bone mineral density in Caucasian men and women.

U2 - 10.1016/j.bone.2012.07.022

DO - 10.1016/j.bone.2012.07.022

M3 - Article

VL - 51

SP - 939

EP - 943

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -