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

被引:80
作者
Hamshere, Marian L. [1 ]
Stergiakouli, Evangelia [1 ]
Langley, Kate [1 ]
Martin, Joanna [1 ]
Holmans, Peter [1 ]
Kent, Lindsey [2 ]
Owen, Michael J. [1 ]
Gill, Michael [3 ]
Thapar, Anita [1 ]
O'Donovan, Mick [1 ]
Craddock, Nick [1 ]
机构
[1] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales
[2] Univ St Andrews, Bute Med Sch, St Andrews KY16 9AJ, Fife, Scotland
[3] Trinity Ctr Hlth Sci, Dept Psychiat, Dublin, Ireland
基金
英国惠康基金; 英国医学研究理事会;
关键词
GENOME-WIDE ASSOCIATION; RISK; COMMON; VARIANTS; PARENTS; ADHD;
D O I
10.1192/bjp.bp.112.117432
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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 x 10(-4), 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 x 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.
引用
收藏
页码:107 / 111
页数:5
相关论文
共 28 条
[1]   The efficacy of 2 different dosages of methylphenidate in treating adults with attention-deficit hyperactivity disorder [J].
Bouffard, R ;
Hechtman, L ;
Minde, K ;
Iaboni-Kassab, F .
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE, 2003, 48 (08) :546-554
[2]   Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].
Burton, Paul R. ;
Clayton, David G. ;
Cardon, Lon R. ;
Craddock, Nick ;
Deloukas, Panos ;
Duncanson, Audrey ;
Kwiatkowski, Dominic P. ;
McCarthy, Mark I. ;
Ouwehand, Willem H. ;
Samani, Nilesh J. ;
Todd, John A. ;
Donnelly, Peter ;
Barrett, Jeffrey C. ;
Davison, Dan ;
Easton, Doug ;
Evans, David ;
Leung, Hin-Tak ;
Marchini, Jonathan L. ;
Morris, Andrew P. ;
Spencer, Chris C. A. ;
Tobin, Martin D. ;
Attwood, Antony P. ;
Boorman, James P. ;
Cant, Barbara ;
Everson, Ursula ;
Hussey, Judith M. ;
Jolley, Jennifer D. ;
Knight, Alexandra S. ;
Koch, Kerstin ;
Meech, Elizabeth ;
Nutland, Sarah ;
Prowse, Christopher V. ;
Stevens, Helen E. ;
Taylor, Niall C. ;
Walters, Graham R. ;
Walker, Neil M. ;
Watkins, Nicholas A. ;
Winzer, Thilo ;
Jones, Richard W. ;
McArdle, Wendy L. ;
Ring, Susan M. ;
Strachan, David P. ;
Pembrey, Marcus ;
Breen, Gerome ;
St Clair, David ;
Caesar, Sian ;
Gordon-Smith, Katherine ;
Jones, Lisa ;
Fraser, Christine ;
Green, Elain K. .
NATURE, 2007, 447 (7145) :661-678
[3]   The Kraepelinian dichotomy - going, going ... but still not gone [J].
Craddock, Nick ;
Owen, Michael J. .
BRITISH JOURNAL OF PSYCHIATRY, 2010, 196 (02) :92-95
[4]   Dissecting the phenotype in genome-wide association studies of psychiatric illness [J].
Craddock, Nick ;
Kerdler, Kenneth ;
Neale, Michael ;
Nurnberger, John ;
Purcell, Shaun ;
Rietschel, Marcella ;
Perlis, Roy ;
Santangelo, Susan L. ;
Schulze, Thomas ;
Smoller, Jordan W. ;
Thapar, Anita .
BRITISH JOURNAL OF PSYCHIATRY, 2009, 195 (02) :97-99
[5]   Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility [J].
Evans, David M. ;
Spencer, Chris C. A. ;
Pointon, Jennifer J. ;
Su, Zhan ;
Harvey, David ;
Kochan, Grazyna ;
Opperman, Udo ;
Dilthey, Alexander ;
Pirinen, Matti ;
Stone, Millicent A. ;
Appleton, Louise ;
Moutsianis, Loukas ;
Leslie, Stephen ;
Wordsworth, Tom ;
Kenna, Tony J. ;
Karaderi, Tugce ;
Thomas, Gethin P. ;
Ward, Michael M. ;
Weisman, Michael H. ;
Farrar, Claire ;
Bradbury, Linda A. ;
Danoy, Patrick ;
Inman, Robert D. ;
Maksymowych, Walter ;
Gladman, Dafna ;
Rahman, Proton ;
Morgan, Ann ;
Marzo-Ortega, Helena ;
Bowness, Paul ;
Gaffney, Karl ;
Gaston, J. S. Hill ;
Smith, Malcolm ;
Bruges-Armas, Jacome ;
Couto, Ana-Rita ;
Sorrentino, Rosa ;
Paladini, Fabiana ;
Ferreira, Manuel A. ;
Xu, Huji ;
Liu, Yu ;
Jiang, Lei ;
Lopez-Larrea, Carlos ;
Diaz-Pena, Roberto ;
Lopez-Vazquez, Antonio ;
Zayats, Tetyana ;
Band, Gavin ;
Bellenguez, Celine ;
Blackburn, Hannah ;
Blackwell, Jenefer M. ;
Bramon, Elvira ;
Bumpstead, Suzannah J. .
NATURE GENETICS, 2011, 43 (08) :761-U67
[6]   Polygenic dissection of the bipolar phenotype [J].
Hamshere, M. L. ;
O'Donovan, M. C. ;
Jones, I. R. ;
Jones, L. ;
Kirov, G. ;
Green, E. K. ;
Moskvina, V. ;
Grozeva, D. ;
Bass, N. ;
McQuillin, A. ;
Gurling, H. ;
St Clair, D. ;
Young, A. H. ;
Ferrier, I. N. ;
Farmer, A. ;
McGuffin, P. ;
Sklar, P. ;
Purcell, S. ;
Holmans, P. A. ;
Owen, M. J. ;
Craddock, N. .
BRITISH JOURNAL OF PSYCHIATRY, 2011, 198 (04) :284-288
[7]   Genome-Wide Association Study of Schizophrenia in a Japanese Population [J].
Ikeda, Masashi ;
Aleksic, Branko ;
Kinoshita, Yoko ;
Okochi, Tomo ;
Kawashima, Kunihiro ;
Kushima, Itaru ;
Ito, Yoshihito ;
Nakamura, Yukako ;
Kishi, Taro ;
Okumura, Takenori ;
Fukuo, Yasuhisa ;
Williams, Hywel J. ;
Hamshere, Marian L. ;
Ivanov, Dobril ;
Inada, Toshiya ;
Suzuki, Michio ;
Hashimoto, Ryota ;
Ujike, Hiroshi ;
Takeda, Masatoshi ;
Craddock, Nick ;
Kaibuchi, Kozo ;
Owen, Michael J. ;
Ozaki, Norio ;
O'Donovan, Michael C. ;
Iwata, Nakao .
BIOLOGICAL PSYCHIATRY, 2011, 69 (05) :472-478
[8]   Psychopathology among offspring of parents with schizophrenia: Relationship to premorbid impairments [J].
Keshavan, Matcheri ;
Montrose, Debra M. ;
Rajarethinam, Rajaprabhakaran ;
Diwadkar, Vaibhav ;
Prasad, Konasale ;
Sweeney, John A. .
SCHIZOPHRENIA RESEARCH, 2008, 103 (1-3) :114-120
[9]   Psychosis proneness and ADHD in young relatives of schizophrenia patients [J].
Keshaven, MS ;
Sujata, M ;
Mehra, A ;
Montrose, DM ;
Sweeney, JA .
SCHIZOPHRENIA RESEARCH, 2003, 59 (01) :85-92
[10]   Bipolar disorder risk alleles in adult ADHD patients [J].
Landaas, E. T. ;
Johansson, S. ;
Halmoy, A. ;
Oedegaard, K. J. ;
Fasmer, O. B. ;
Haavik, J. .
GENES BRAIN AND BEHAVIOR, 2011, 10 (04) :418-423