Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, China.
J Dev Orig Health Dis. 2024 Jun 3;15:e12. doi: 10.1017/S2040174424000114.
Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight ( = 298,142) and childhood obesity ( = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium ( = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.
肥胖与骨关节炎（OA）有关，但很少有研究使用胎儿起源来探索这种关联。我们的研究旨在使用孟德尔随机化（MR）来厘清出生体重、儿童肥胖与成人 OA 之间的因果关系。我们从早期生长遗传学联盟（Early Growth Genetics Consortium）贡献的两项全基因组关联研究中确定了与出生体重（=298142）和儿童肥胖（=24160）相关的单核苷酸多态性（SNP）。来自骨关节炎遗传学联盟（Genetics of Osteoarthritis Consortium）的 OA 及其表型（膝关节、髋关节、脊柱、手部、拇指和手指 OA）的汇总统计数据（=826690）用于估计 SNP 对 OA 的影响。多变量 MR（MVMR）用于研究暴露的独立影响。结果表明，出生体重的遗传预测标准差增加与 OA 无关。相比之下，儿童肥胖与总 OA 呈正相关[比值比（OR）=1.07，95%置信区间（CI）=1.00，1.15 使用 IVW]、膝关节 OA（OR=1.13，95%CI=1.05，1.22 使用加权中位数）、髋关节 OA（OR=1.13，95%CI=1.04，1.24 使用 IVW）和脊柱 OA（OR=1.12，95%CI=1.03，1.22 使用 IVW），但与手部、拇指或手指 OA 无关。MVMR 表明儿童肥胖与 OA 之间存在潜在的成年体重指数依赖因果途径。总之，出生体重与 OA 之间没有关联。然而，儿童肥胖与承重关节 OA 之间存在因果关系，这似乎是肥胖与 OA 的一般关联。
