摘要：
背景：先前的研究表明童年期虐待与哮喘之间可能存在关联。为此，我们设计了一项孟德尔随机化（MR）研究以进一步探究这一关联。
方法：利用孟德尔随机化（MR）方法，我们基于英国生物样本库（UK Biobank, UKB）的全基因组关联研究（GWAS）数据。主要结局指标为哮喘，通过两项独立研究的GWAS数据集（AsthmaUKB和AsthmaIEU）进行分析。此外，我们针对儿童期哮喘和成人期哮喘进行了分层分析。使用逆方差加权法（IVW）、MR-Egger法和MR-PRESSO检验评估童年期虐待（CM）对哮喘的因果影响。
结果：IVW分析发现童年期虐待（CM）与AsthmaUKB（OR=1.59, 95% CI=1.23-2.05, p<0.001）、AsthmaIEU（OR=1.04,95% CI=1.02-1.06,p<0.001）、儿童期哮喘（OR=1.72,95% CI=1.26-2.35, p=0.001）以及成人期哮喘（OR=1.71, 95% CI=1.17-2.48, p=0.005）的风险增加存在显著关联。MR-Egger和MR-PRESSO结果证实不存在多效性，从而加强了我们的因果推断。尽管Cochran's Q检验表明哮喘亚型间存在一定异质性（p>0.05），IVW结果的稳健性仍然可靠。
结论：本研究通过孟德尔随机化分析验证了童年期虐待与多种哮喘表型存在潜在因果关系，强调CM应纳入哮喘防治策略，为解析生命早期逆境致哮喘的病因通路奠定基础。
Exploring the causal link between childhood maltreatment and asthma: a Mendelian randomization study
Z.Zhang, Y. T. Wang, J. Z. Li, H. Ren, X. L. Wang, H. T. Qiu, et al.
Abstract
BACKGROUND:
Prior research indicates a potential connection between childhood maltreatment and asthma. In response, we designed a Mendelian Randomization (MR) study to further investigate this association.
METHODS:
Utilizing the MR approach, we leveraged Genome-Wide Association Studies (GWAS) data from the UK Biobank (UKB). Our primary outcome was asthma, analyzed through GWAS datasets termed AsthmaUKB and AsthmaIEU, sourced from two distinct studies. Additionally, we conducted stratified analyses focusing on pediatric asthma and adult asthma to address different asthma phenotypes. The causal impact of childhood maltreatment (CM) on asthma was assessed using inverse-variance weighted (IVW) methods, MR-Egger, and MR-PRESSO tests, thereby enhancing the robustness and generalizability of our findings.
RESULTS:
The IVW analyses identified significant associations between CM and increased risks for AsthmaUKB (OR = 1.59, 95% CI = 1.23-2.05, p < .001), AsthmaIEU (OR = 1.04, 95% CI = 1.02-1.06, p < .001), pediatric asthma (OR = 1.72, 95% CI = 1.26-2.35, p = .001), and adult asthma (OR = 1.71, 95% CI = 1.17-2.48, p = .005). The MR-Egger and MR-PRESSO results confirmed the absence of pleiotropy, reinforcing our causal inferences. Although Cochran's Q test indicated some heterogeneity among asthma subtypes (p > .05), the robustness of the IVW results remains reliable.
CONCLUSION:
Our findings suggest a potential causal relationship between CM and various asthma phenotypes, as validated through rigorous Mendelian randomization analyses. These results emphasize the importance of considering CM in asthma prevention and intervention strategies and lay the groundwork for further investigation into how early-life adversities may predispose individuals to asthma, contributing to a deeper understanding of its etiological pathways.
背景：先前的研究表明童年期虐待与哮喘之间可能存在关联。为此，我们设计了一项孟德尔随机化（MR）研究以进一步探究这一关联。
方法：利用孟德尔随机化（MR）方法，我们基于英国生物样本库（UK Biobank, UKB）的全基因组关联研究（GWAS）数据。主要结局指标为哮喘，通过两项独立研究的GWAS数据集（AsthmaUKB和AsthmaIEU）进行分析。此外，我们针对儿童期哮喘和成人期哮喘进行了分层分析。使用逆方差加权法（IVW）、MR-Egger法和MR-PRESSO检验评估童年期虐待（CM）对哮喘的因果影响。
结果：IVW分析发现童年期虐待（CM）与AsthmaUKB（OR=1.59, 95% CI=1.23-2.05, p<0.001）、AsthmaIEU（OR=1.04,95% CI=1.02-1.06,p<0.001）、儿童期哮喘（OR=1.72,95% CI=1.26-2.35, p=0.001）以及成人期哮喘（OR=1.71, 95% CI=1.17-2.48, p=0.005）的风险增加存在显著关联。MR-Egger和MR-PRESSO结果证实不存在多效性，从而加强了我们的因果推断。尽管Cochran's Q检验表明哮喘亚型间存在一定异质性（p>0.05），IVW结果的稳健性仍然可靠。
结论：本研究通过孟德尔随机化分析验证了童年期虐待与多种哮喘表型存在潜在因果关系，强调CM应纳入哮喘防治策略，为解析生命早期逆境致哮喘的病因通路奠定基础。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（European Journal of Psychotraumatology 2025 Vol. 16 Issue 1 DOI: Artn 238312710.1080/20008066.2024.2383127）
Exploring the causal link between childhood maltreatment and asthma: a Mendelian randomization study
Z.Zhang, Y. T. Wang, J. Z. Li, H. Ren, X. L. Wang, H. T. Qiu, et al.
Abstract
BACKGROUND:
Prior research indicates a potential connection between childhood maltreatment and asthma. In response, we designed a Mendelian Randomization (MR) study to further investigate this association.
METHODS:
Utilizing the MR approach, we leveraged Genome-Wide Association Studies (GWAS) data from the UK Biobank (UKB). Our primary outcome was asthma, analyzed through GWAS datasets termed AsthmaUKB and AsthmaIEU, sourced from two distinct studies. Additionally, we conducted stratified analyses focusing on pediatric asthma and adult asthma to address different asthma phenotypes. The causal impact of childhood maltreatment (CM) on asthma was assessed using inverse-variance weighted (IVW) methods, MR-Egger, and MR-PRESSO tests, thereby enhancing the robustness and generalizability of our findings.
RESULTS:
The IVW analyses identified significant associations between CM and increased risks for AsthmaUKB (OR = 1.59, 95% CI = 1.23-2.05, p < .001), AsthmaIEU (OR = 1.04, 95% CI = 1.02-1.06, p < .001), pediatric asthma (OR = 1.72, 95% CI = 1.26-2.35, p = .001), and adult asthma (OR = 1.71, 95% CI = 1.17-2.48, p = .005). The MR-Egger and MR-PRESSO results confirmed the absence of pleiotropy, reinforcing our causal inferences. Although Cochran's Q test indicated some heterogeneity among asthma subtypes (p > .05), the robustness of the IVW results remains reliable.
CONCLUSION:
Our findings suggest a potential causal relationship between CM and various asthma phenotypes, as validated through rigorous Mendelian randomization analyses. These results emphasize the importance of considering CM in asthma prevention and intervention strategies and lay the groundwork for further investigation into how early-life adversities may predispose individuals to asthma, contributing to a deeper understanding of its etiological pathways.
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