Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort
Abstract Background ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms unde...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-023-09498-6 |
| _version_ | 1797453880766758912 |
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| author | Quanfa He Taylor J. Keding Qi Zhang Jiacheng Miao Justin D. Russell Ryan J. Herringa Qiongshi Lu Brittany G. Travers James J. Li |
| author_facet | Quanfa He Taylor J. Keding Qi Zhang Jiacheng Miao Justin D. Russell Ryan J. Herringa Qiongshi Lu Brittany G. Travers James J. Li |
| author_sort | Quanfa He |
| collection | DOAJ |
| description | Abstract Background ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms underlying ADHD. We leveraged functional annotation information into an ADHD PGS to (1) improve the prediction performance over a non-annotated ADHD PGS and (2) test whether volumetric variation in brain regions putatively associated with ADHD mediate the association between PGSs and ADHD outcomes. Methods Data were from the Philadelphia Neurodevelopmental Cohort (N = 555). Multiple mediation models were tested to examine the indirect effects of two ADHD PGSs—one using a traditional computation involving clumping and thresholding and another using a functionally annotated approach (i.e., AnnoPred)—on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Results A direct effect was detected between the AnnoPred ADHD PGS and IA symptoms in adolescents. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, both ADHD PGSs were negatively associated with the DLPFC. Conclusions The AnnoPred ADHD PGS was a more developmentally specific predictor of adolescent IA symptoms compared to the traditional ADHD PGS. However, brain volumes did not mediate the effects of either a traditional or AnnoPred ADHD PGS on ADHD symptoms, suggesting that we may still be underpowered in clarifying brain-based biomarkers for ADHD using genetic measures. |
| first_indexed | 2024-03-09T15:29:16Z |
| format | Article |
| id | doaj.art-60c2a1bb613c459ba1a32da05e7d5a4c |
| institution | Directory Open Access Journal |
| issn | 1866-1955 |
| language | English |
| last_indexed | 2024-03-09T15:29:16Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-60c2a1bb613c459ba1a32da05e7d5a4c2023-11-26T12:22:21ZengBMCJournal of Neurodevelopmental Disorders1866-19552023-08-0115111210.1186/s11689-023-09498-6Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohortQuanfa He0Taylor J. Keding1Qi Zhang2Jiacheng Miao3Justin D. Russell4Ryan J. Herringa5Qiongshi Lu6Brittany G. Travers7James J. Li8Department of Psychology, University of, Wisconsin-MadisonDepartment of Psychology, Yale UniversityDepartment of Educational Psychology, University of Wisconsin-MadisonDepartment of Biostatistics and Medical Informatics, University of Wisconsin-MadisonDepartment of Psychiatry, School of Medicine and Public Health, University of WisconsinDepartment of Psychiatry, School of Medicine and Public Health, University of WisconsinDepartment of Biostatistics and Medical Informatics, University of Wisconsin-MadisonWaisman Center, University of Wisconsin-MadisonDepartment of Psychology, University of, Wisconsin-MadisonAbstract Background ADHD polygenic scores (PGSs) have been previously shown to predict ADHD outcomes in several studies. However, ADHD PGSs are typically correlated with ADHD but not necessarily reflective of causal mechanisms. More research is needed to elucidate the neurobiological mechanisms underlying ADHD. We leveraged functional annotation information into an ADHD PGS to (1) improve the prediction performance over a non-annotated ADHD PGS and (2) test whether volumetric variation in brain regions putatively associated with ADHD mediate the association between PGSs and ADHD outcomes. Methods Data were from the Philadelphia Neurodevelopmental Cohort (N = 555). Multiple mediation models were tested to examine the indirect effects of two ADHD PGSs—one using a traditional computation involving clumping and thresholding and another using a functionally annotated approach (i.e., AnnoPred)—on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Results A direct effect was detected between the AnnoPred ADHD PGS and IA symptoms in adolescents. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, both ADHD PGSs were negatively associated with the DLPFC. Conclusions The AnnoPred ADHD PGS was a more developmentally specific predictor of adolescent IA symptoms compared to the traditional ADHD PGS. However, brain volumes did not mediate the effects of either a traditional or AnnoPred ADHD PGS on ADHD symptoms, suggesting that we may still be underpowered in clarifying brain-based biomarkers for ADHD using genetic measures.https://doi.org/10.1186/s11689-023-09498-6ADHDPolygenic scoresBrain volumeFunctional annotationMultiple mediation |
| spellingShingle | Quanfa He Taylor J. Keding Qi Zhang Jiacheng Miao Justin D. Russell Ryan J. Herringa Qiongshi Lu Brittany G. Travers James J. Li Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort Journal of Neurodevelopmental Disorders ADHD Polygenic scores Brain volume Functional annotation Multiple mediation |
| title | Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort |
| title_full | Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort |
| title_fullStr | Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort |
| title_full_unstemmed | Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort |
| title_short | Neurogenetic mechanisms of risk for ADHD: Examining associations of polygenic scores and brain volumes in a population cohort |
| title_sort | neurogenetic mechanisms of risk for adhd examining associations of polygenic scores and brain volumes in a population cohort |
| topic | ADHD Polygenic scores Brain volume Functional annotation Multiple mediation |
| url | https://doi.org/10.1186/s11689-023-09498-6 |
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