脑沟形态特征与骨坏死风险的孟德尔随机化分析

doi:10.3877/cma.j.issn.1674-134X.2025.05.008

目的

本研究旨在探讨大脑脑沟形态（如脑沟深度与开口距离）与骨坏死之间的因果关联，为骨坏死的病理机制研究及高风险人群的早期筛查提供新视角。

方法

本研究采用两样本孟德尔随机化设计，利用与脑沟深度与沟开口距离相关的遗传变异作为工具变量，通过英国NHGRI-EBI和芬兰FinnGen数据库的全基因组关联数据进行分析。逆方差加权法（IVW）为主要分析方法，并通过多种敏感性分析验证结果的稳健性。

结果

研究发现，在44种脑沟形态特征中，仅右侧前下颞沟的沟开口距离与骨坏死存在显著的负向因果关联[比值比（OR）=0.348，95%置信区间（CI）（0.143，0.847），P=0.020]，提示右侧前下颞沟的沟开口距离增加可能降低骨坏死风险。其他脑沟特征未显示统计学意义的关联（均为P>0.05）。

结论

右侧前下颞沟的脑沟开口距离与骨坏死之间存在可能的因果关联，提示脑沟形态特征可作为骨坏死的潜在生物标志物筛查高风险人群。

关键词: 大脑皮层, 骨坏死, 孟德尔随机化分析, 因果律

Objective

To investigate the causal relationship between sulcal morphology (specifically sulcal depth and opening distance) and osteonecrosis through Mendelian randomization analysis, thereby providing new perspectives for research on osteonecrosis pathogenesis and early screening of high-risk populations.

Methods

A two-sample Mendelian randomization design was employed, using genetic variants associated with sulcal depth as instrumental variables. Data were derived from large-scale GWAS datasets in the NHGRI-EBI and FinnGen repositories. The primary analysis was conducted using the inverse variance-weighted (IVW) method, with sensitivity analyses to validate the robustness of the findings.

Results

Among 44 sulcal features analyzed, only the sulcal opening depth of the right anterior inferior temporal sulcus was significantly associated with osteonecrosis, showing a negative causal relationship [odds ratio (OR) =0.348, 95% confidence interval (CI) (0.143, 0.847), P=0.020]. Other sulcal features demonstrated no statistically significant associations (all P>0.05).

Conclusion

There might be a causal link between the sulcal depth of the right anterior inferior temporal sulcus and osteonecrosis, which suggests sulcal depth as a potential biomarker for osteonecrosis screening in at-risk population.

Key words: Cerebral cortex, Osteonecrosis, Mendelian randomization, Causality

图1 44种脑沟形态特征与骨坏死之间随机因果关联注：SD-脑沟深度；SOD-脑沟沟开口距离；L/R-左/右；此图由chiplot绘制

Figure 1 Causal effects between 44 morphology features and osteonecrosis riskNote: SD-sulcal depth; SOD-sulcal opening distance; L/R-left/right; drawn by chiplot

图2 右侧前下颞沟的沟开口距离与骨坏死随机因果关系MR（孟德尔随机化）分析。图A为散点图；图B为漏斗图；图C为"留一法"分析森林图

Figure 2 MR (Mendelian randomization) analysis of the causal relationship between sulcal opening distance of the right anterior inferior temporal sulcus and osteonecrosis. A is scatter plot; B is funnel plot; C is forest plot of leave-one-out sensitivity analysis

表1 特定脑沟形态特征与骨坏死之间随机因果关联

Table 1 Causal associations between specific sulcal morphology features and osteonecrosis

结局Outcom	暴露Exposure	ID	分析方法Methods	SNPs	β值	SE	OR（95%CI）	P值
骨坏死Osteonecrosis	右侧前下颞沟的沟开口距离	GCST90104947	IVW	15	-1.055	0.453	0.3481（0.143，0.847）	<0.05
			BWMR		-1.085	0.478	0.338（0.132，0.862）	<0.05
			RAPS		-1.074	0.498	0.342（0.129，0.907）	<0.05
			DIVW		-1.101	0.478	0.333（0.130，0.849）	<0.05

表1 特定脑沟形态特征与骨坏死之间随机因果关联

Table 1 Causal associations between specific sulcal morphology features and osteonecrosis

结局Outcom	暴露Exposure	ID	分析方法Methods	SNPs	β值	SE	OR（95%CI）	P值
骨坏死Osteonecrosis	右侧前下颞沟的沟开口距离	GCST90104947	IVW	15	-1.055	0.453	0.3481（0.143，0.847）	<0.05
			BWMR		-1.085	0.478	0.338（0.132，0.862）	<0.05
			RAPS		-1.074	0.498	0.342（0.129，0.907）	<0.05
			DIVW		-1.101	0.478	0.333（0.130，0.849）	<0.05

表2 敏感性分析结果

Table 2 Sensitivity analysis results

结局Outcome	暴露Exposure	ID	异质性检验Heterogeneity test				水平多效性测试Horizontal pleiotropic test			MR-PRESSO
结局Outcome	暴露Exposure	ID	方法Methods	Q	Q_df	Q_pval	Egger截距Egger intercept	SE	P值	全局测试P值P of global test
骨坏死Osteonecros-is	右侧前下颞沟的沟开口距离	GCST90104947	MR Egger	7.745	13	0.860	-0.001	0.026	0.955	0.9200
骨坏死Osteonecros-is	右侧前下颞沟的沟开口距离	GCST90104947	IVW	7.749	14	0.902	-0.001	0.026	0.955	0.9200

表2 敏感性分析结果

Table 2 Sensitivity analysis results

结局Outcome	暴露Exposure	ID	异质性检验Heterogeneity test				水平多效性测试Horizontal pleiotropic test			MR-PRESSO
结局Outcome	暴露Exposure	ID	方法Methods	Q	Q_df	Q_pval	Egger截距Egger intercept	SE	P值	全局测试P值P of global test
骨坏死Osteonecros-is	右侧前下颞沟的沟开口距离	GCST90104947	MR Egger	7.745	13	0.860	-0.001	0.026	0.955	0.9200
骨坏死Osteonecros-is	右侧前下颞沟的沟开口距离	GCST90104947	IVW	7.749	14	0.902	-0.001	0.026	0.955	0.9200

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Mendelian randomization analysis of sulcal morphology and osteonecrosis risk

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Mendelian randomization analysis of sulcal morphology and osteonecrosis risk