Center of System Biomedical Sciences, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, PR China.
PLoS One. 2013 Apr 4;8(4):e60362. doi: 10.1371/journal.pone.0060362. Print 2013.
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.
股骨颈几何参数（FNGP），包括皮质厚度（CT）、骨膜直径（W）、弯曲比（BR）、横截面积（CSA）和截面模数（Z），有助于骨骼强度，并可能预测髋部骨折风险。初潮年龄（AAM）是女性骨质疏松症和骨折的重要危险因素。一些 FNGP 与 AAM 存在遗传相关性。在这项研究中，我们进行了双变量全基因组关联研究（GWAS），以鉴定与 FNGP 和 AAM 均相关的新候选基因。在发现阶段，我们在 1728 名无血缘关系的白种人受试者中测试了 760794 个 SNP，随后在美国白种人（501 名受试者）和中国人（826 名受试者）的独立样本中进行了复制分析。我们发现了六个与 FNGP 和 AAM 相关的 SNP。这些 SNP 位于三个基因（即 NRCAM、IDS 和 LOC148145）中，表明这三个基因可能共同调节 FNGP 和 AAM。我们的研究结果可能有助于提高对骨质疏松症和 AAM 遗传结构和病理生理机制的理解。
