Skip to main content

Advertisement

SpringerLink
Log in

Genome-wide pathway analysis in attention-deficit/hyperactivity disorder

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

This study aimed to (1) to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of attention-deficit/hyperactivity disorder (ADHD) and (2) to generate SNP-to-gene-to-pathway hypotheses. An ADHD genome-wide association study (GWAS) dataset that included 428,074 SNPs in 924 trios (2,758 individuals) of European descent was used in this study. The Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 11 candidate SNPs, 6 genes, and 6 pathways, which provided 6 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was that rs2532502 alters the role of CD27 in the context of the pathways of positive regulation of nucleocytoplasmic transport [nominal p < 0.001; false discovery rate (FDR) = 0.028]. The second strongest mechanism was the rs1820204, rs1052571, rs1052576 → CASP9 → mitochondrial pathway (nominal p < 0.001; FDR = 0.032). The third mechanism was the rs1801516 → ATM → CD25 pathway (nominal p < 0.001; FDR = 0.034). By applying the ICSNPathway analysis to the ADHD GWAS data, 11 candidate SNPs, 6 genes that included CD27, CASP9, ATM, CD12orf65, OXER1, and ACRY, and 6 pathways were identified that may contribute to ADHD susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Franke B, Faraone SV, Asherson P, Buitelaar J, Bau CH, Ramos-Quiroga JA, Mick E, Grevet EH, Johansson S, Haavik J, Lesch KP, Cormand B, Reif A, International Multicentre Persistent ADHD Collaboration (2012) The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry 17:960–987

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Manolio TA (2010) Genomewide association studies and assessment of the risk of disease. N Engl J Med 363:166–176

    Article  CAS  PubMed  Google Scholar 

  3. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45:166–170

    Article  CAS  Google Scholar 

  4. Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118:434–443

    Article  PubMed  Google Scholar 

  5. Johnson AD, O’Donnell CJ (2009) An open access database of genome-wide association results. BMC Med Genet 10:6

    Article  PubMed Central  PubMed  Google Scholar 

  6. Boomsma DI, Willemsen G, Sullivan PF, Heutink P, Meijer P, Sondervan D, Kluft C, Smit G, Nolen WA, Zitman FG, Smit JH, Hoogendijk WJ, van Dyck R, de Geus EJ, Penninx BW (2008) Genome-wide association of major depression: description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects. Eur J Hum Genet 16:335–342

    Article  CAS  PubMed  Google Scholar 

  7. Wang K, Li M, Hakonarson H (2010) Analysing biological pathways in genome-wide association studies. Nat Rev Genet 11:843–854

    Article  CAS  PubMed  Google Scholar 

  8. Lee YH, Song GG (2012) Pathway analysis of genome-wide association studies on uric acid concentrations. Hum Immunol 73:805–810

    Article  CAS  PubMed  Google Scholar 

  9. Zhang K, Chang S, Cui S, Guo L, Zhang L, Wang J (2011) ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework. Nucleic Acids Res 39:W437–W443

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Kuntsi J, Neale BM, Chen W, Faraone SV, Asherson P (2006) The IMAGE project: methodological issues for the molecular genetic analysis of ADHD. Behav Brain Funct 2:27

    Article  PubMed Central  PubMed  Google Scholar 

  11. Coghill D, Banaschewski T (2009) The genetics of attention-deficit/hyperactivity disorder. Expert Rev Neurother 9:1547–1565

    Article  CAS  PubMed  Google Scholar 

  12. Croft M (2009) The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9:271–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Wurstle ML, Laussmann MA, Rehm M (2012) The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome. Exp Cell Res 318:1213–1220

    Article  CAS  PubMed  Google Scholar 

  14. Carlessi L, Fusar Poli E, De Filippis L, Delia D (2013) ATM-deficient human neural stem cells as an in vitro model system to study neurodegeneration. DNA Repair (Amst) 12(8):605–611

    Article  CAS  Google Scholar 

  15. Duarte I, Nabuurs SB, Magno R, Huynen M (2012) Evolution and diversification of the organellar release factor family. Mol Biol Evol 29:3497–3512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Pardo CA, Vargas DL, Zimmerman AW (2005) Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 17:485–495

    Article  PubMed  Google Scholar 

  18. Balestrieri E, Pitzianti M, Matteucci C, D’Agati E, Sorrentino R, Baratta A, Caterina R, Zenobi R, Curatolo P, Garaci E, Sinibaldi-Vallebona P, Pasini A (2013) Human endogenous retroviruses and ADHD. World J Biol Psychiatry. doi:10.3109/15622975.2013.862345

  19. Mann JR, McDermott S (2011) Are maternal genitourinary infection and pre-eclampsia associated with ADHD in school-aged children? J Atten Disord 15:667–673

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no vested interest that could be construed to have inappropriately influenced this study.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 5 ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee & Gwan Gyu Song

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.H., Song, G.G. Genome-wide pathway analysis in attention-deficit/hyperactivity disorder. Neurol Sci 35, 1189–1196 (2014). https://doi.org/10.1007/s10072-014-1671-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-014-1671-2

Keywords

Search

Navigation