Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study

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 genet...

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Bibliographic Details
Published in:PloS one 2008-09, Vol.3 (9), p.e3160-e3160
Main Authors: Liu, Yao-Zhong, Wilson, Scott G, Wang, Liang, Liu, Xiao-Gang, Guo, Yan-Fang, Li, Jian, Yan, Han, Deloukas, Panos, Soranzo, Nicole, Chinappen-Horsley, Usha, Chinnapen-Horsley, Usha, Cervino, Alessandra, Cervino, Alesandra, Williams, Frances M, Xiong, Dong-Hai, Zhang, Yin-Ping, Jin, Tian-Bo, Levy, Shawn, Papasian, Christopher J, Drees, Betty M, Hamilton, James J, Recker, Robert R, Spector, Tim D, Deng, Hong-Wen
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Adaptor Proteins, Signal Transducing - physiology
Algorithms
Analysis
Biocompatibility
Bioinformatics
Biomedical materials
Body Mass Index
Body Size
Calcium
Calcium signalling
China
College campuses
Cytokines
Education
Engineering
Epidemiology
Female
Females
Fractures
Fractures, Bone - metabolism
Fractures, Bone - pathology
Gene Expression Regulation
Genes
Genetic factors
Genetics
Genetics and Genomics
Genetics and Genomics/Complex Traits
Genetics and Genomics/Functional Genomics
Genome, Human
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Genotyping
Health aspects
Health risks
Hip
Hospitals
Humans
Inositol 1,4,5-trisphosphate receptors
Laboratories
Life sciences
Male
Males
Medicine
Morbidity
Mortality
Older people
Osteoporosis
Osteoporosis - etiology
Osteoporosis - genetics
Pathogenesis
Pelvic Bones - anatomy & histology
Phospholipase
Phospholipase C
Polymorphism, Single Nucleotide
Recombinant Proteins - metabolism
Retailing
Risk analysis
Risk Factors
Schizophrenia
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Studies
Trauma
United Kingdom
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Summary: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 approximately 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 3.72x10(-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 8.62x10(-3) and 2.44x10(-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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0003160