Cortical structure and the risk for Alzheimer's disease: a bidirectional Mendelian randomization study.

Translational Psychiatry
Bang-Sheng WuJin-Tai Yu


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 th...Continue Reading


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