Skip to main content
×
×
Home

Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia

  • Marian L. Hamshere (a1), Evangelia Stergiakouli (a1), Kate Langley (a1), Joanna Martin (a1), Peter Holmans (a1), Lindsey Kent (a2), Michael J. Owen (a1), Michael Gill (a3), Anita Thapar (a1), Mick O'Donovan (a1) and Nick Craddock (a1)...
Extract
Background

There is recent evidence of some degree of shared genetic susceptibility between adult schizophrenia and childhood attention-deficit hyperactivity disorder (ADHD) for rare chromosomal variants.

Aims

To determine whether there is overlap between common alleles conferring risk of schizophrenia in adults with those that do so for ADHD in children.

Method

We used recently published Psychiatric Genome-wide Association Study (GWAS) Consortium (PGC) adult schizophrenia data to define alleles over-represented in people with schizophrenia and tested whether those alleles were more common in 727 children with ADHD than in 2067 controls.

Results

Schizophrenia risk alleles discriminated ADHD cases from controls (P = 1.04 × 104, R 2 = 0.45%); stronger discrimination was given by alleles that were risk alleles for both adult schizophrenia and adult bipolar disorder (also derived from a PGC data-set) (P = 9.98 ×10−6, R 2 × 0.59%).

Conclusions

This increasing evidence for a small, but significant, shared genetic susceptibility between adult schizophrenia and childhood ADHD highlights the importance of research work across traditional diagnostic boundaries.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia
      Available formats
      ×
Copyright
Corresponding author
Professor N. Craddock, Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. Email: CraddockN@cardiff.ac.uk.
Footnotes
Hide All

See editorial, pp. 81–83, this issue.

Declaration of interest

None.

Footnotes
References
Hide All
1 Owen, MJ, Craddock, N, O'Donovan, MC. Suggestion of roles for both common and rare risk variants in genome-wide studies of schizophrenia. Arch Gen Psychiatry 2010; 67: 667–73.
2 Craddock, N, Owen, MJ. The Kraepelinian dichotomy – going, going … but still not gone. Br J Psychiatry 2010; 196: 92–5.
3 Craddock, N, Kendler, K, Neale, M, Nurnberger, J, Purcell, S, Rietschel, M, et al Dissecting the phenotype in genome-wide association studies of psychiatric illness. Br J Psychiatry 2009; 195: 97–9.
4 Williams, NM, Zaharieva, I, Martin, A, Langley, K, Mantripragada, K, Fossdal, R, et al Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 2010; 376: 1401–8.
5 Landaas, ET, Johansson, S, Halmoy, A, Oedegaard, KJ, Fasmer, OB, Haavik, J. Bipolar disorder risk alleles in adult ADHD patients. Genes Brain Behav 2011; 10: 418–23.
6 Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, et al Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–52.
7 Ripke, S, Sanders, AR, Kendler, KS, Levinson, DF, Sklar, P, Holmans, PA, et al Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969–76.
8 Sklar, P, Ripke, S, Scott, LJ, Andreassen, OA, Cichon, S, Craddock, N, et al Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011; 43: 977–83.
9 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447: 661–78.
10 Stergiakouli, E, Hamshere, M, Holmans, P, Langley, K, Zaharieva, I, Hawi, Z, et al Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am J Psychiatry 2012; 169: 186–94.
11 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). APA, 1987.
12 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). APA, 1994.
13 World Health Organization. The ICD–10 Classification of Mental and Behavioural Disorders. WHO, 1992.
14 Evans, DM, Spencer, CC, Pointon, JJ, Su, Z, Harvey, D, Kochan, G, et al Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet 2011; 43: 761–7.
15 O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, et al Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 2008; 40: 1053–5.
16 Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MA, Bender, D, et al PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–75.
17 Patterson, N, Price, AL, Reich, D. Population structure and eigenanalysis. PLoS Genet 2006; 2: e190.
18 Price, AL, Patterson, NJ, Plenge, RM, Weinblatt, ME, Shadick, NA, Reich, D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38: 904–9.
19 Rieder, RO, Nichols, PL. Offspring of schizophrenics. III. Hyperactivity and neurological soft signs. Arch Gen Psychiatry 1979; 36: 665–74.
20 Oner, O, Munir, K. Attentional and neurocognitive characteristics of high-risk offspring of parents with schizophrenia compared with DSM-IV attention deficit hyperactivity disorder children. Schizophr Res 2005; 76: 293–9.
21 Keshavan, MS, Sujata, M, Mehra, A, Montrose, DM, Sweeney, JA. Psychosis proneness and ADHD in young relatives of schizophrenia patients. Schizophr Res 2003; 59: 8592.
22 Keshavan, M, Montrose, DM, Rajarethinam, R, Diwadkar, V, Prasad, K, Sweeney, JA. Psychopathology among offspring of parents with schizophrenia: relationship to premorbid impairments. Schizophr Res 2008; 103: 114–20.
23 Peralta, V, de Jalon, EG, Campos, MS, Zandio, M, Sanchez-Torres, A, Cuesta, MJ. The meaning of childhood attention-deficit hyperactivity symptoms in patients with a first-episode of schizophrenia-spectrum psychosis. Schizophr Res 2011; 126: 2835.
24 Hamshere, ML, O'Donovan, MC, Jones, IR, Jones, L, Kirov, G, Green, EK, et al Polygenic dissection of the bipolar phenotype. Br J Psychiatry 2011; 198: 284–8.
25 Ruderfer, DM, Kirov, G, Chambert, K, Moran, JL, Owen, MJ, O'Donovan, MC, et al A family-based study of common polygenic variation and risk of schizophrenia. Mol Psychiatry 2011; 16: 887–8.
26 Ikeda, M, Aleksic, B, Kinoshita, Y, Okochi, T, Kawashima, K, Kushima, I, et al Genome-wide association study of schizophrenia in a Japanese population. Biol Psychiatry 2011; 69: 472–8.
27 Lee, SH, Decandia, TR, Ripke, S, Yang, J, Sullivan, PF, Goddard, ME, et al Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 2012; 44: 247–50.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Shared polygenic contribution between childhood attention-deficit hyperactivity disorder and adult schizophrenia

  • Marian L. Hamshere (a1), Evangelia Stergiakouli (a1), Kate Langley (a1), Joanna Martin (a1), Peter Holmans (a1), Lindsey Kent (a2), Michael J. Owen (a1), Michael Gill (a3), Anita Thapar (a1), Mick O'Donovan (a1) and Nick Craddock (a1)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *