التفاصيل البيبلوغرافية
| العنوان: |
Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes. |
| المؤلفون: |
Olfson, Emily, Farhat, Luis C., Liu, Wenzhong, Vitulano, Lawrence A., Zai, Gwyneth, Lima, Monicke O., Parent, Justin, Polanczyk, Guilherme V., Cappi, Carolina, Kennedy, James L., Fernandez, Thomas V. |
| المصدر: |
Nature Communications; 7/12/2024, Vol. 15 Issue 1, p1-10, 10p |
| مصطلحات موضوعية: |
ATTENTION-deficit hyperactivity disorder, DNA damage, BIRTHPARENTS, DNA sequencing, GENES, DNA adducts, WNT signal transduction |
| مستخلص: |
Research demonstrates the important role of genetic factors in attention-deficit/hyperactivity disorder (ADHD). DNA sequencing of families provides a powerful approach for identifying de novo (spontaneous) variants, leading to the discovery of hundreds of clinically informative risk genes for other childhood neurodevelopmental disorders. This approach has yet to be extensively leveraged in ADHD. We conduct whole-exome DNA sequencing in 152 families, comprising a child with ADHD and both biological parents, and demonstrate a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in ADHD cases compared to unaffected controls. Combining these results with a large independent case-control DNA sequencing cohort (3206 ADHD cases and 5002 controls), we identify lysine demethylase 5B (KDM5B) as a high-confidence risk gene for ADHD and estimate that 1057 genes contribute to ADHD risk. Using our list of genes harboring ultra-rare de novo damaging variants, we show that these genes overlap with previously reported risk genes for other neuropsychiatric conditions and are enriched in several canonical biological pathways, suggesting early neurodevelopmental underpinnings of ADHD. This work provides insight into the biology of ADHD and demonstrates the discovery potential of DNA sequencing in larger parent-child trio cohorts. Here, whole-exome DNA sequencing study of parent-child trios shows a significant enrichment of rare and ultra-rare de novo gene-damaging mutations in children with ADHD compared to unaffected controls and identifies KDM5B as a high-confidence risk gene. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Find this article in full text from Springer Verlag. 
Full Text Finder