The causal impact of childhood obesity on bone mineral density and fracture in adulthood: A two-sample Mendelian randomization study

Abstract

Observational studies have indicated the associations between obesity with bone mineral density (BMD) and fracture but yield inconsistent results. The impact of childhood obesity on bone health in adulthood is even less clear. The present study adopted the Mendelian randomization methods to determine whether the genetically predicted childhood obesity was causally associated with BMD and the risk of fracture. Genetic variants were extracted from genome-wide association studies (GWAS) to identify childhood obesity loci [IEU open GWAS project: childhood obesity (ID: ieu-a-1096)] and single nucleotide polymorphisms (SNPs) as instrumental variables to investigate causality. We used two-sample univariable Mendelian randomization (MR) to estimate causal relationships between childhood obesity on BMD and fracture subtypes based on SNPs from European samples. To avoid bias, Cochran's Q test and leave-one-out variant analysis were performed. The MR analysis shows strong evidence that childhood obesity is causally associated with eBMD (OR 1.068, 95% CI 1.043–1.095, P < 0.001) and a weak decreased risk of leg fracture (OR 0.9990, 95% CI 0.9981–0.9999, P =0.033) based on the inverse variance weighting (IVW) method. After adjusting for diabetes and adult obesity, the results of eBMD remained the same. The MR analysis revealed sufficient evidence to indicate childhood obesity was causally associated with increased BMD and decreased risk of leg fracture in adults. Childhood obesity could be taken into consideration when assessing eBMD.

Causal effects of life course adiposity on temporomandibular disorders: A Mendelian randomization study

“…The differential effects of BMI throughout the life course on TMDs align with biological plausibility. Firstly, low BMI in children may hinder the growth and development of the TMJ, while the associated structures have typically reached maturity by adulthood, thereby diminishing the impact of BMI on TMDs 37 . Secondly, adults may be more susceptible to socioeconomic and competitive pressures, which could exert a stronger influence on TMDs compared to adiposity itself 8 .…”

“…Firstly, low BMI in children may hinder the growth and development of the TMJ, while the associated structures have typically reached maturity by adulthood, thereby diminishing the impact of BMI on TMDs. 37 Secondly, adults may be more susceptible to socioeconomic and competitive pressures, which could exert a stronger influence on TMDs compared to adiposity itself. 8 It is worth noting that directly examining the effects of BMI, body size and body fat percentage on TMDs within the framework of multivariable MR analysis is challenging due to the high genetic correlation among these factors.…”

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring

“…The genome‐wide association test was conducted with adjustments for age, sex, study location, genetic principal components, relatedness, and other study‐specific characteristics. Independent SNPs that were not in linkage disequilibrium (LD), defined by a distance greater than 10 000 kb and R 2 ≤ 0.001 as previously described (Liang et al., 2022), were included. The SNPs with the highest correlation between each locus and AD maternal medical history were selected to generate IVs.…”