Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study

Y-Z. Liu, Scott Wilson, L. Wang, X-G. Liu, Y-F. Guo, J. Li, H. Yan, P. Deloukas, N. Soranzo, U. Chinnapen-Horsley, A. Cervino, F.M. Williams, D-H. Xiong, Y-P. Zhang, T-B. Jin, S. Levy, C.J. Papasian, B.M. Drees, J.J. Hamilton, R.R. Recker & 2 others T.D. Spector, H-W. Deng

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Abstract

Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ~380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values
Original languageEnglish
Pages (from-to)online - approx 5-20pp
JournalPLoS One
Volume3
Issue number9
DOIs
Publication statusPublished - 2008

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Pelvic Bones
Phospholipases
Genome-Wide Association Study
hips
Single Nucleotide Polymorphism
Bone
Genes
bones
hip fractures
genes
Hip Fractures
developmental orthopedic disease
Metabolic Bone Diseases
osteoporosis
genotyping
Osteoporosis
morbidity
phospholipases
genome-wide association study
risk factors

Cite this

Liu, Y-Z. ; Wilson, Scott ; Wang, L. ; Liu, X-G. ; Guo, Y-F. ; Li, J. ; Yan, H. ; Deloukas, P. ; Soranzo, N. ; Chinnapen-Horsley, U. ; Cervino, A. ; Williams, F.M. ; Xiong, D-H. ; Zhang, Y-P. ; Jin, T-B. ; Levy, S. ; Papasian, C.J. ; Drees, B.M. ; Hamilton, J.J. ; Recker, R.R. ; Spector, T.D. ; Deng, H-W. / Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study. In: PLoS One. 2008 ; Vol. 3, No. 9. pp. online - approx 5-20pp.
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abstract = "Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ~380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values",
author = "Y-Z. Liu and Scott Wilson and L. Wang and X-G. Liu and Y-F. Guo and J. Li and H. Yan and P. Deloukas and N. Soranzo and U. Chinnapen-Horsley and A. Cervino and F.M. Williams and D-H. Xiong and Y-P. Zhang and T-B. Jin and S. Levy and C.J. Papasian and B.M. Drees and J.J. Hamilton and R.R. Recker and T.D. Spector and H-W. Deng",
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Liu, Y-Z, Wilson, S, Wang, L, Liu, X-G, Guo, Y-F, Li, J, Yan, H, Deloukas, P, Soranzo, N, Chinnapen-Horsley, U, Cervino, A, Williams, FM, Xiong, D-H, Zhang, Y-P, Jin, T-B, Levy, S, Papasian, CJ, Drees, BM, Hamilton, JJ, Recker, RR, Spector, TD & Deng, H-W 2008, 'Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study' PLoS One, vol. 3, no. 9, pp. online - approx 5-20pp. https://doi.org/10.1371/journal.pone.0003160

Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study. / Liu, Y-Z.; Wilson, Scott; Wang, L.; Liu, X-G.; Guo, Y-F.; Li, J.; Yan, H.; Deloukas, P.; Soranzo, N.; Chinnapen-Horsley, U.; Cervino, A.; Williams, F.M.; Xiong, D-H.; Zhang, Y-P.; Jin, T-B.; Levy, S.; Papasian, C.J.; Drees, B.M.; Hamilton, J.J.; Recker, R.R.; Spector, T.D.; Deng, H-W.

In: PLoS One, Vol. 3, No. 9, 2008, p. online - approx 5-20pp.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of PLCL1 Gene for Hip Bone Size Variation in Females in a Genome-Wide Association Study

AU - Liu, Y-Z.

AU - Wilson, Scott

AU - Wang, L.

AU - Liu, X-G.

AU - Guo, Y-F.

AU - Li, J.

AU - Yan, H.

AU - Deloukas, P.

AU - Soranzo, N.

AU - Chinnapen-Horsley, U.

AU - Cervino, A.

AU - Williams, F.M.

AU - Xiong, D-H.

AU - Zhang, Y-P.

AU - Jin, T-B.

AU - Levy, S.

AU - Papasian, C.J.

AU - Drees, B.M.

AU - Hamilton, J.J.

AU - Recker, R.R.

AU - Spector, T.D.

AU - Deng, H-W.

PY - 2008

Y1 - 2008

N2 - Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ~380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values

AB - Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating ~380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72×10−7. The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62×10−3 and 2.44×10−3, respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values

U2 - 10.1371/journal.pone.0003160

DO - 10.1371/journal.pone.0003160

M3 - Article

VL - 3

SP - online - approx 5-20pp

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 9

ER -