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

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    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",
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    doi = "10.1016/j.bone.2012.07.022",
    language = "English",
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    pages = "939--943",
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    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 -