目的·通过两样本孟德尔随机化（Mendelian randomization，MR）研究阐述阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）与脑成像衍生表型（imaging-derived phenotype，IDP）之间的因果关系。方法·OSA的相关遗传数据来自芬兰基因生物银行R11（FinnGen Biobank）中的全基因组关联研究（genome⁃wide association study，GWAS），其中，病例组50 200例，对照组401 484例；从中筛选出27个单核苷酸多态性（single⁃nucleotide polymorphism，SNP）作为OSA的工具变量。3 935种IDP的GWAS来自英国生物样本库（UK Biobank）39 691名欧洲血统个体的多模态神经影像数据。采用逆方差加权（inverse variance weighted，IVW）为主的多种MR方法进行分析，并进行异质性、多效性和敏感性检验。结果·MR分析显示8种IDP与OSA的发生显著相关，例如右侧半球额中回尾部体积显著增加OSA风险，体积每增加1个标准差对应于OSA风险增高11% （IVW方法的OR=1.11，95%CI 1.06~1.17，P<0.001）。而OSA可能与1种IDP呈负相关（IVW β=-0.10，95%CI -0.19~-0.01，P=0.025）。这种IDP属于静息态功能连接特征，是双侧额极与右侧额顶皮层的功能连接强度。异质性检验提示工具变量之间未发现显著异质性，多效性检验未检测到多效性，敏感性分析提示结果稳定。结论·8种IDP可能与OSA的发生显著相关，而其中1种IDP与OSA的发生呈负相关，为非侵入式神经调控治疗OSA提供了潜在靶点。

Objective ·To elucidate the causal relationship between obstructive sleep apnea (OSA) and imaging-derived phenotypes (IDPs) through two-sample Mendelian randomization (MR) studies. Methods ·The genetic data related to OSA were obtained from the genome-wide association study (GWAS) (n_{case group}=50 200, n_{control group}=401 484) in the FinnGen Biobank R11. Twenty-seven single nucleotide polymorphisms (SNPs) were screened out as instrumental variables of OSA. The GWAS of 3 935 IDPs was based on multimodal neuroimaging data from 39 691 individuals of European ancestry in the UK Biobank. Multiple MR methods, primarily utilizing inverse variance weighted (IVW) analysis, were applied, along with assessments for heterogeneity, pleiotropy, and sensitivity. Results ·MR analysis indicated that 8 IDPs were associated with OSA. For example, the genetically determined volume of caudal middle frontal gyrus in the right hemisphere was associated with an increased risk of OSA. A one‒standard-deviation increase in volume corresponded to an 11% higher risk of OSA (IVW OR=1.11, 95%CI 1.06‒1.17, P<0.001). Genetically determined reduced risk of OSA was associated with a resting-state functional connectivity characteristic (IVW β=-0.10, 95%CI -0.19‒-0.01, P=0.025), representing the functional connectivity strength between the bilateral frontal poles and the right frontal-parietal cortex. The heterogeneity test did not find significant heterogeneity among the instrumental variables. The pleiotropy test did not detect any pleiotropy. The sensitivity analysis indicated stable results. Conclusion ·Eight IDPs may have a causal relationship with the occurrence of OSA, among which one IDP shows a bidirectional causal relationship, providing potential targets for non-invasive neuromodulation interventions in OSA.