Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0003160
Title: Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study
Authors: Liu Y.-Z.
Wilson S.G.
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.
Keywords: calcium ion
gene product
inositol 1,4,5 trisphosphatase
phospholipase C like 1 protein
unclassified drug
magic factor 1 protein, mouse
magic-factor 1 protein, mouse
recombinant protein
signal transducing adaptor protein
adult
aged
article
bone cell
bone structure
calcium signaling
Caucasian
Chinese
cohort analysis
controlled study
female
gene function
gene identification
gene replication
genetic association
genetic risk
genetic variability
genome analysis
genotype
hip fracture
human
major clinical study
male
pathogenesis
regulatory mechanism
single nucleotide polymorphism
body mass
body size
China
fracture
gene expression regulation
genetics
histology
human genome
metabolism
osteoporosis
pathology
pelvic girdle
physiology
risk factor
United Kingdom
Adaptor Proteins, Signal Transducing
Body Mass Index
Body Size
China
Female
Fractures, Bone
Gene Expression Regulation
Genome, Human
Great Britain
Humans
Male
Osteoporosis
Pelvic Bones
Polymorphism, Single Nucleotide
Recombinant Proteins
Risk Factors
Issue Date: 2008
Citation: Liu Y.-Z., Wilson S.G., 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. (2008). Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study. PLoS ONE 3 (9) : e3160. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0003160
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�-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�-3 and 2.44�-3, respectively, for association with hip S. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10-5 in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only ?0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66�-3 (odds ratio = 0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a ovel gene associated with variation in Hip BS, and provide new insights into the pathogenesis of HF. � 2008 Liu et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161849
ISSN: 19326203
DOI: 10.1371/journal.pone.0003160
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0003160.pdf426.9 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

42
checked on Dec 9, 2019

Page view(s)

10
checked on Dec 5, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.