Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder

作者：Yilu Zhao, Zhao Fu, Eric J. Barnett, Ning Wang, Kangfuxi Zhang, Xuping Gao, Xiangyu Zheng, Junbin Tian, Hui Zhang, Xue-Tong Ding, Shaoxian Li, Shuyu Li, Qingjiu Cao, Suhua Chang, Yufeng Wang, Stephen V. Faraone, Li Yang · 发表于：Translational Psychiatry · 年份：2025 · DOI：10.1038/s41398-025-03250-5 · 被引用次数：4 · 研究领域：Attention Deficit Hyperactivity Disorder

Although the efficacy of pharmacy in the treatment of attention deficit/hyperactivity disorder (ADHD) has been well established, the lack of predictors of treatment response poses great challenges for personalized treatment. The current study employed a comprehensive approach, combining genome-wide association analyses (GWAS) and deep learning (DL) methods, to elucidate the genetic underpinnings of pharmacological treatment response in ADHD. Based on genotype data of medication-naïve patients with ADHD who received pharmacological treatments for 12 weeks, the current study performed GWAS using the percentage changes in ADHD-RS score as phenotype. Then, DL models were constructed to predict percentage changes in symptom scores using genetic variants selected based on four different genome-wide P thresholds (E-02, E-03, E-04, E-05) as inputs. The current GWAS results identified two significant loci (rs10880574, P = 2.39E-09; rs2000900, P = 3.31E-09) which implicated two genes, TMEM117 and MYO5B, that were primarily associated with both brain- and gut-related disorders. The convolutional neural network (CNN) model, using variants with genome-wide P values less than E-02 (5516 SNPs), demonstrated the best performance with mean squared error (MSE) equals 0.012 (Accuracy = 0.83; Sensitivity = 0.90; Specificity = 0.75) in the validation dataset, 0.081 in an independent test dataset (Acc = 0.61, Sensitivity = 0.81; Specificity = 0.26). Notably, the variant that contributed most to th...