Cortical structure and the risk for Alzheimer's disease: a bidirectional Mendelian randomization study.
Cortical structure and the risk for Alzheimer's disease: a bidirectional Mendelian randomization study.
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皮质结构和阿尔茨海默氏病的风险：双向孟德尔随机化研究。
DOI：
10.1038/s41398-021-01599-x
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发表时间：
2021-09-15
影响因子：
6.8
通讯作者：
Yu JT
中科院分区：
文献类型：
--
作者：
Wu BS;Zhang YR;Li HQ;Kuo K;Chen SD;Dong Q;Liu Y;Yu JT
阿尔茨海默病(AD)的表现之一是特定脑区神经元的进行性丢失。很多工作都致力于研究脑萎缩和阿尔茨海默病。然而，皮质结构与AD之间的因果关系尚不清楚。我们进行了双向两样本孟德尔随机分析，以调查皮质结构(整个皮质和34个皮质区域的表面积和厚度)与AD风险之间的因果关系。用作工具的遗传变异来自对皮质结构(33,992名欧洲血统参与者)和AD(AD和替代AD，71,880例，383,378例对照)的大型全基因组联合荟萃分析。我们发现颞极表面积减少(OR(95%CI)：0.95(0.9，0.997)，p = 0.04)和楔骨厚度减少(OR(95%CI)：0.93(0.89，0.98)，p = 0.006)与AD风险增加有关。我们还发现AD的易感性与中央前核(β(SE)：-43.421.3，p = 0.042)和峡部扣带回(β(SE)：-18.57.3，p = 0.011)的表面积减少有关。然而，经Bonferroni校正的皮质结构与AD之间因果关系的p值均未达到阈值。我们提供了一些提示性证据，表明颞极和楔骨萎缩与AD风险较高有关。在另一个方向，AD易感性与中央前叶和峡部扣带回表面积的减少之间存在可能的因果关系。我们的发现揭示了大脑皮层结构与AD发生的关系。
Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.
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影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
DOI：
10.1016/j.nicl.2017.04.001
发表时间：
2017
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Ramos Bernardes da Silva Filho S;Oliveira Barbosa JH;Rondinoni C;Dos Santos AC;Garrido Salmon CE;da Costa Lima NK;Ferriolli E;Moriguti JC
通讯作者：
Moriguti JC
影响因子：
4.6
作者：
Ferreira D;Verhagen C;Hernández-Cabrera JA;Cavallin L;Guo CJ;Ekman U;Muehlboeck JS;Simmons A;Barroso J;Wahlund LO;Westman E
通讯作者：
Westman E
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
25
作者：
Fu H;Hardy J;Duff KE
通讯作者：
Duff KE