Wen Junhao, Skampardoni Ioanna, Tian Ye Ella, Yang Zhijian, Cui Yuhan, Erus Guray, Hwang Gyujoon, Varol Erdem, Boquet-Pujadas Aleix, Chand Ganesh B, Nasrallah Ilya M, Satterthwaite Theodore D, Shou Haochang, Shen Li, Toga Arthur W, Zalesky Andrew, Davatzikos Christos
Laboratory of AI and Biomedical Science (LABS), Columbia University, New York, NY, USA.
Department of Radiology, Columbia University, New York, NY, USA.
Nat Biomed Eng. 2025 Jun 6. doi: 10.1038/s41551-025-01412-w.
Recent work leveraging artificial intelligence has offered promise to dissect disease heterogeneity by identifying complex intermediate brain phenotypes, called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine DNEs derived from independent yet harmonized studies on Alzheimer's disease, autism spectrum disorder, late-life depression and schizophrenia in the UK Biobank study. Phenome-wide associations align with genome-wide associations, revealing 31 genomic loci (P < 5 × 10/9) associated with the nine DNEs. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors and chronic diseases.
最近利用人工智能开展的研究有望通过识别复杂的中间脑表型(即维度神经影像内表型,DNEs)来剖析疾病异质性。我们进一步论证,这些DNEs反映了所测量的各神经解剖模式的表达程度,为研究神经疾病和神经精神疾病的疾病异质性及相似性提供了一种维度神经解剖学表征。我们在英国生物银行研究中调查了源自关于阿尔茨海默病、自闭症谱系障碍、老年期抑郁症和精神分裂症的独立但统一研究的9种DNEs的存在情况。全表型关联与全基因组关联一致,揭示了与这9种DNEs相关的31个基因组位点(P < 5 × 10/9)。这9种DNEs及其多基因风险评分显著提高了对14种全身性疾病类别的预测准确性,尤其是与心理健康和中枢神经系统相关的疾病以及死亡结局。这些发现强调了这9种DNEs在捕捉普通人群个体中疾病相关脑表型的表达以及将这些测量结果与遗传学、生活方式因素和慢性疾病相关联方面的潜力。