Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder
Abstract 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 gen...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03250-5 |
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| author | Yilu Zhao Zhao Fu Eric J. Barnett Ning Wang Kangfuxi Zhang Xuping Gao Xiangyu Zheng Junbin Tian Hui Zhang XueTong Ding Shaoxian Li Shuyu Li Qingjiu Cao Suhua Chang Yufeng Wang Stephen V. Faraone Li Yang |
| author_facet | Yilu Zhao Zhao Fu Eric J. Barnett Ning Wang Kangfuxi Zhang Xuping Gao Xiangyu Zheng Junbin Tian Hui Zhang XueTong Ding Shaoxian Li Shuyu Li Qingjiu Cao Suhua Chang Yufeng Wang Stephen V. Faraone Li Yang |
| author_sort | Yilu Zhao |
| collection | DOAJ |
| description | Abstract 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 the CNN model was NKAIN2, an ADHD-related gene, which is also associated with metabolic processes. To conclude, the integration of GWAS and DL methods revealed new genes contribute to ADHD pharmacological treatment responses, and underscored the interplay between neural systems and metabolic processes, potentially providing critical insights into precision treatment. Furthermore, our CNN model exhibited good performance in an independent dataset, encouraged future studies and implied potential clinical applications. |
| format | Article |
| id | doaj-art-d13317a927974829adb159872c2206ac |
| institution | Kabale University |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-d13317a927974829adb159872c2206ac2025-02-09T12:55:34ZengNature Publishing GroupTranslational Psychiatry2158-31882025-02-0115111010.1038/s41398-025-03250-5Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorderYilu Zhao0Zhao Fu1Eric J. Barnett2Ning Wang3Kangfuxi Zhang4Xuping Gao5Xiangyu Zheng6Junbin Tian7Hui Zhang8XueTong Ding9Shaoxian Li10Shuyu Li11Qingjiu Cao12Suhua Chang13Yufeng Wang14Stephen V. Faraone15Li Yang16Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)School of Engineering Medicine, Beihang UniversitySchool of Engineering Medicine, Beihang UniversityState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal UniversityState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders, (Peking University S+ixth Hospital), NHC Key Laboratory of Mental Health (Peking University)Abstract 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 the CNN model was NKAIN2, an ADHD-related gene, which is also associated with metabolic processes. To conclude, the integration of GWAS and DL methods revealed new genes contribute to ADHD pharmacological treatment responses, and underscored the interplay between neural systems and metabolic processes, potentially providing critical insights into precision treatment. Furthermore, our CNN model exhibited good performance in an independent dataset, encouraged future studies and implied potential clinical applications.https://doi.org/10.1038/s41398-025-03250-5 |
| spellingShingle | Yilu Zhao Zhao Fu Eric J. Barnett Ning Wang Kangfuxi Zhang Xuping Gao Xiangyu Zheng Junbin Tian Hui Zhang XueTong Ding Shaoxian Li Shuyu Li Qingjiu Cao Suhua Chang Yufeng Wang Stephen V. Faraone Li Yang Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder Translational Psychiatry |
| title | Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| title_full | Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| title_fullStr | Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| title_full_unstemmed | Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| title_short | Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| title_sort | genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder |
| url | https://doi.org/10.1038/s41398-025-03250-5 |
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