Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding re...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2073-4425/12/2/310 |
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| author | Yichuan Liu Xiao Chang Hui-Qi Qu Lifeng Tian Joseph Glessner Jingchun Qu Dong Li Haijun Qiu Patrick Sleiman Hakon Hakonarson |
| author_facet | Yichuan Liu Xiao Chang Hui-Qi Qu Lifeng Tian Joseph Glessner Jingchun Qu Dong Li Haijun Qiu Patrick Sleiman Hakon Hakonarson |
| author_sort | Yichuan Liu |
| collection | DOAJ |
| description | Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA. Multiple novel rare recurrent variants were identified in exonic regions, functionally classified as stop-gains and frameshifts for known ADHD genes. Deletion in introns of the protocadherins families and the ncRNA <i>HGB8P</i> were identified in two independent EA ADHD patients. A meta-analysis of the two ethnicities for differential ADHD recurrent variants compared to controls shows a small number of overlaps. These results suggest that rare recurrent variants in noncoding regions may be involved in the pathogenesis of ADHD in children of both AA and EA ancestry; thus, WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD. |
| first_indexed | 2024-03-09T00:37:55Z |
| format | Article |
| id | doaj.art-ea4ec1b8a4a344b4b33a3540a481c162 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T00:37:55Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ea4ec1b8a4a344b4b33a3540a481c1622023-12-11T18:02:11ZengMDPI AGGenes2073-44252021-02-0112231010.3390/genes12020310Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American AncestryYichuan Liu0Xiao Chang1Hui-Qi Qu2Lifeng Tian3Joseph Glessner4Jingchun Qu5Dong Li6Haijun Qiu7Patrick Sleiman8Hakon Hakonarson9Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USACenter for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAAttention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA. Multiple novel rare recurrent variants were identified in exonic regions, functionally classified as stop-gains and frameshifts for known ADHD genes. Deletion in introns of the protocadherins families and the ncRNA <i>HGB8P</i> were identified in two independent EA ADHD patients. A meta-analysis of the two ethnicities for differential ADHD recurrent variants compared to controls shows a small number of overlaps. These results suggest that rare recurrent variants in noncoding regions may be involved in the pathogenesis of ADHD in children of both AA and EA ancestry; thus, WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD.https://www.mdpi.com/2073-4425/12/2/310attention-deficit hyperactivity disorderwhole genome sequencenoncoding regionsgenetic variants |
| spellingShingle | Yichuan Liu Xiao Chang Hui-Qi Qu Lifeng Tian Joseph Glessner Jingchun Qu Dong Li Haijun Qiu Patrick Sleiman Hakon Hakonarson Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry Genes attention-deficit hyperactivity disorder whole genome sequence noncoding regions genetic variants |
| title | Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry |
| title_full | Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry |
| title_fullStr | Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry |
| title_full_unstemmed | Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry |
| title_short | Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry |
| title_sort | rare recurrent variants in noncoding regions impact attention deficit hyperactivity disorder adhd gene networks in children of both african american and european american ancestry |
| topic | attention-deficit hyperactivity disorder whole genome sequence noncoding regions genetic variants |
| url | https://www.mdpi.com/2073-4425/12/2/310 |
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