Open AccessBivariate Genome-Wide Association Analyses Identified Genes with Pleiotropic Effects for Femoral Neck Bone Geometry and Age at Menarche
Author(s) -
Shu Ran,
YuFang Pei,
Yongjun Liu,
Lei Zhang,
Yingying Han,
Rong Hai,
Qing Tian,
Yong Lin,
TieLin Yang,
Yan-Fang Guo,
Hui Shen,
Inderpal S. Thethi,
Xinyao Zhu,
HongWen Deng
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0060362
Subject(s) - femoral neck , genome wide association study , menarche , single nucleotide polymorphism , osteoporosis , medicine , bone density , genetics , biology , gene , bioinformatics , genotype
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.