title: Bivariate genome-wide association analyses identified genes with pleiotropic effects for femoral neck bone geometry and age at menarche.
abstract: Femoral neck geometric parameters (FNGPs), which include cortical thickness (CT), periosteal diameter (W), buckling ratio (BR), cross-sectional area (CSA), and section modulus (Z), contribute to bone strength and may predict hip fracture risk. Age at menarche (AAM) is an important risk factor for osteoporosis and bone fractures in women. Some FNGPs are genetically correlated with AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both FNGPs and AAM. In the discovery stage, we tested 760,794 SNPs in 1,728 unrelated Caucasian subject, followed by replication analyses in independent samples of US Caucasians (with 501 subjects) and Chinese (with 826 subjects). We found six SNPs that were associated with FNGPs and AAM. These SNPs are located in three genes (i.e. NRCAM, IDS and LOC148145), suggesting these three genes may co-regulate FNGPs and AAM. Our findings may help improve the understanding of genetic architecture and pathophysiological mechanisms underlying both osteoporosis and AAM.
authors.affiliation: Center of System Biomedical Sciences, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Ran
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Pei
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Han
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Inderpal S
authors.initials: IS
authors.lastname: Thethi
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008572:Menarche / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult