Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0003160
DC FieldValue
dc.titleIdentification of PLCL1 gene for hip bone size variation in females in a genome-wide association study
dc.contributor.authorLiu Y.-Z.
dc.contributor.authorWilson S.G.
dc.contributor.authorWang L.
dc.contributor.authorLiu X.-G.
dc.contributor.authorGuo Y.-F.
dc.contributor.authorLi J.
dc.contributor.authorYan H.
dc.contributor.authorDeloukas P.
dc.contributor.authorSoranzo N.
dc.contributor.authorChinnapen-Horsley U.
dc.contributor.authorCervino A.
dc.contributor.authorWilliams F.M.
dc.contributor.authorXiong D.-H.
dc.contributor.authorZhang Y.-P.
dc.contributor.authorJin T.-B.
dc.contributor.authorLevy S.
dc.contributor.authorPapasian C.J.
dc.contributor.authorDrees B.M.
dc.contributor.authorHamilton J.J.
dc.contributor.authorRecker R.R.
dc.contributor.authorSpector T.D.
dc.contributor.authorDeng H.-W.
dc.date.accessioned2019-11-08T00:55:26Z
dc.date.available2019-11-08T00:55:26Z
dc.date.issued2008
dc.identifier.citationLiu 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
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161849
dc.description.abstractOsteoporosis, 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.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectcalcium ion
dc.subjectgene product
dc.subjectinositol 1,4,5 trisphosphatase
dc.subjectphospholipase C like 1 protein
dc.subjectunclassified drug
dc.subjectmagic factor 1 protein, mouse
dc.subjectmagic-factor 1 protein, mouse
dc.subjectrecombinant protein
dc.subjectsignal transducing adaptor protein
dc.subjectadult
dc.subjectaged
dc.subjectarticle
dc.subjectbone cell
dc.subjectbone structure
dc.subjectcalcium signaling
dc.subjectCaucasian
dc.subjectChinese
dc.subjectcohort analysis
dc.subjectcontrolled study
dc.subjectfemale
dc.subjectgene function
dc.subjectgene identification
dc.subjectgene replication
dc.subjectgenetic association
dc.subjectgenetic risk
dc.subjectgenetic variability
dc.subjectgenome analysis
dc.subjectgenotype
dc.subjecthip fracture
dc.subjecthuman
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectpathogenesis
dc.subjectregulatory mechanism
dc.subjectsingle nucleotide polymorphism
dc.subjectbody mass
dc.subjectbody size
dc.subjectChina
dc.subjectfracture
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjecthistology
dc.subjecthuman genome
dc.subjectmetabolism
dc.subjectosteoporosis
dc.subjectpathology
dc.subjectpelvic girdle
dc.subjectphysiology
dc.subjectrisk factor
dc.subjectUnited Kingdom
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectBody Mass Index
dc.subjectBody Size
dc.subjectChina
dc.subjectFemale
dc.subjectFractures, Bone
dc.subjectGene Expression Regulation
dc.subjectGenome, Human
dc.subjectGreat Britain
dc.subjectHumans
dc.subjectMale
dc.subjectOsteoporosis
dc.subjectPelvic Bones
dc.subjectPolymorphism, Single Nucleotide
dc.subjectRecombinant Proteins
dc.subjectRisk Factors
dc.typeArticle
dc.contributor.departmentDEPT OF CHEMISTRY
dc.description.doi10.1371/journal.pone.0003160
dc.description.sourcetitlePLoS ONE
dc.description.volume3
dc.description.issue9
dc.description.pagee3160
Appears in Collections:Staff Publications
Elements

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

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons