Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Bone. 2021 Feb;143:115792. doi: 10.1016/j.bone.2020.115792. Epub 2020 Dec 4.
Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape.
Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2.
Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta -0.05, p = 9.9 × 10; age 18: -0.05, p = 3.3 × 10) and HSM5 (age 14: beta -0.07, p = 1.6 × 10; age 18: -0.1, p = 2.7 × 10). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 × 10; age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: -0.06, p = 0.001; age 18: -0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture.
In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life.
髋形是公认的髋关节骨关节炎（OA）和髋部骨折的危险因素。我们旨在研究与成人髋形相关的遗传变异是否也与青少年髋形相关。
使用来自阿冯纵向研究父母和儿童（ALSPAC）的后代在两个时间点（平均年龄 13.8 岁和 17.8 岁）获得的髋部 DXA 扫描，使用 53 个点的统计形状模型（SSM）定量髋部形态。主成分分析用于生成髋形模式（HSM）。先前显示与成人特定 HSM 存在全基因组显著关联的遗传变异，在青少年中（分别在每个时间点）使用 SNPTEST v2 测试与同一 HSM 的关联。
在 14 岁和 18 岁时，分别有 3550 名和 3175 名个体具有完整的基因型和表型数据。与青少年髋形关联最强的证据是位于 SOX9 附近的变体（rs2158915），在两个时间点上，HSM1（14 岁：β-0.05，p=9.9×10；18 岁：β-0.05，p=3.3×10）和 HSM5（14 岁：β-0.07，p=1.6×10；18 岁：β-0.1，p=2.7×10）的效应一致。rs10743612（靠近 PTHLH）和 HSM1（14 岁：0.05，p=1.1×10；18 岁：0.04，p=0.003）之间以及 rs6537291（靠近 HHIP）和 HSM2（14 岁：β-0.06，p=0.001；18 岁：β-0.07，p=0.001）之间也存在强烈的关联。在青少年中与髋形关联最强的基因（SOX9、PTHLH 和 HHIP）已知参与软骨内骨形成。HSM1 表示股骨上部更窄的纵横比，而 HSM2 和 HSM5 均反映了股骨头大小和股骨颈宽度的变化，这些特征以前被发现与晚年 OA 的风险相关。SOX9 基因座先前已被发现与髋部骨折风险增加相关。
总之，与软骨内骨形成相关的变异似乎在青少年和成年期之间持续影响髋形，包括与晚年髋 OA 和/或骨折风险相关的方面。
