Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders

BMC Genomics

卷:22

Research

Weichen Song¹  Wei Qian¹  Weidi Wang²  Guan Ning Lin²  Shunying Yu² 

[1] Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 200030, Shanghai, China;

[2] Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 200030, Shanghai, China;Shanghai Key Laboratory of Psychotic Disorders, 200030, Shanghai, China;

关键词: Neuroimaging;    Neuropsychiatric disorders;    Dysconnectivity;    Anorexia nervosa;    Superior longitudinal fasciculus;   

DOI  :  10.1186/s12864-021-07661-8

 received in 2021-04-25, accepted in 2021-04-29,  发布年份 2021

来源: Springer

【 摘 要 】

BackgroundObservational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown.ResultsHere, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10− 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer’s disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10− 5). By combining all observations, we found that the overall p-value for DTI − Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI − Bipolar disorder (BP) (λ = 2.64) and DTI − AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10− 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation.ConclusionsAs a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.

【 授权许可】

CC BY   
© The Author(s) 2021

【 图 表 】

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