4. Copy number variations as gene candidates in ADHD
Copy number variants (CNVs) are genetic variations that include deletions and duplications of chromosome segments. CNVs occur in less than 1% of the total population. However, they have a major impact on the risk of1
- 4. Copy number variations (CNV) that could be involved in ADHD
- 4.1. 22Q11.2 Duplication / deletion
- 4.2. 2P16.3 (NRXN1)
- 4.3. 15Q11.2 (BP4)
- 4.4. 15Q13.3 (BP4.5-BP5)
- 4.5. 22Q11.21 (COMT)
- 4.6. 1Q21.1 distal
- 4.7. 16P11.2
- 4.8. 16P13.11
- 4.9. 16P13.2
- 4.10. 17Q12 (HNF1B) loss/gain
- 4.11. 16P12.1 (EEF2K, CDR2)
- 4.12. 15Q13.3 (BP 4-5)
- 4.13. 15Q11.2 (BP 1-2)
- 4.14. 2Q11.2 (A-B) loss/gain
- 4.15. 16P11.2 (BP 4-5) loss/gain
- 4.16. TAR (BP 2-3) loss
- 4.17. PWAS (BP 2-3) loss/gain
- 4.18. 16P11.2 (BP 4-5) loss/gain
- 4.19 Int22h1/int22h2-mediated Xq28 duplication syndrome (32 %)
4. Copy number variations (CNV) that could be involved in ADHD
Gene databases:
omim.org and http://www.uniprot.org/
4.1. 22Q11.2 Duplication / deletion
The 22q11.2-deletion syndrome Occurs once in 2150 births, the prevalence of ADHD at 22q11.2Del is around 6% to 37%.5
The 22q11.2-duplication syndrome Occurs once in 1600 births, the ADHD prevalence at 22q11.2Dup is around 18.2 % to 44 %.5
More on this under Monogenetic causes of ADHD.
4.2. 2P16.3 (NRXN1)
Exonic NRXN1 deletions occur in 0.039 to 0.07% of all people and are associated with a 10 to 20% risk of ADHD and an up to 20-fold increased risk of other psychiatric disorders.
More on this under Monogenetic causes of ADHD.
4.3. 15Q11.2 (BP4)
Deletion.2
4.4. 15Q13.3 (BP4.5-BP5)
Deletion.2
4.5. 22Q11.21 (COMT)
Deletion.2
Duplication.2
4.6. 1Q21.1 distal
Duplication.2
1q21.1 (BP 3-4) loss/gain
Duplication.
HR: 2.656
4.7. 16P11.2
proximal
Duplication.2
16p11.2 deletion is one of the most common copy number variations associated with neuronal developmental disorders such as ADHD, ASD and intellectual disability7
4.8. 16P13.11
Duplication.2
16p13.11 (BP 2-3) HR: 2.016
16p13.11 (BP 2-3)
Deletion.
HR: 2.266
4.9. 16P13.2
Source:8
4.10. 17Q12 (HNF1B) loss/gain
Duplication.
HR: 4.196
4.11. 16P12.1 (EEF2K, CDR2)
Deletion.
HR: 1.866
4.12. 15Q13.3 (BP 4-5)
Deletion.
HR: 2.516
4.13. 15Q11.2 (BP 1-2)
Deletion.
HR: 1.436
Duplication.
HR: 1.426
4.14. 2Q11.2 (A-B) loss/gain
Duplication.
HR: 2.616
4.15. 16P11.2 (BP 4-5) loss/gain
Duplication.
HR: 2.636
4.16. TAR (BP 2-3) loss
Duplication.
HR: 1.766
4.17. PWAS (BP 2-3) loss/gain
Duplication.
HR: 3.646
4.18. 16P11.2 (BP 4-5) loss/gain
Duplication.
HR: 2.636
4.19 Int22h1/int22h2-mediated Xq28 duplication syndrome (32 %)
Among males with int22h1/int22h2-mediated Xq28 duplication syndrome, ADHD was found in 32%.10
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Sauter C, Romanos M, Radtke, F (2024): Deletions- und Duplikationssyndrom 22q11.2 und ADHS, neue AKZENTE Nr. 129 3/2024, 10 ↥ ↥
Vaez M, Montalbano S, Calle Sánchez X, Georgii Hellberg KL, Dehkordi SR, Krebs MD, Meijsen J, Shorter J, Bybjerg-Grauholm J, Mortensen PB, Børglum AD, Hougaard DM, Nordentoft M, Geschwind DH, Buil A, Schork AJ, Helenius D, Raznahan A, Thompson WK, Werge T, Ingason A; iPSYCH Investigators (2024): Population-Based Risk of Psychiatric Disorders Associated With Recurrent Copy Number Variants. JAMA Psychiatry. 2024 Oct 1;81(10):957-966. doi: 10.1001/jamapsychiatry.2024.1453. PMID: 38922630; PMCID: PMC11209205. ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥
Kelvington BA, Kim J, Fair R, Gaine ME, Abel T (2025): Complement contributes to hyperactive behavior in the 16p11.2 hemideletion mouse model. bioRxiv [Preprint]. 2025 Aug 21:2025.08.21.671537. doi: 10.1101/2025.08.21.671537. PMID: 40894701; PMCID: PMC12393526. ↥
Gregersen NO, Lydersen LN, Biskopstø M, Zachariasen JF, Jespersen RF, Stórá T, Andorsdóttir G, Wang AG (2024): Whole-exome sequencing implicates 16p13.2 as a risk locus for attention-deficit/hyperactivity disorder in the Faroese population. Psychiatr Genet. 2024 Aug 1;34(4):91. doi: 10.1097/YPG.0000000000000370. PMID: 38958187. ↥
Mitchel MW, Moreno-De-Luca D, Myers SM, Levy RV, Turner S, Ledbetter DH, Martin CL (2016): 17q12 Recurrent Deletion Syndrome. 2016 Dec 8 [updated 2025 Aug 14]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 27929632. REVIEW ↥
Ballout RA, El-Hattab AW, Schaaf CP, Cheung SW (2016): Xq28 Duplication Syndrome, Int22h1/Int22h2 Mediated. 2016 Mar 10 [updated 2025 Sep 4]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 26962617. REVIEW ↥