The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder:: association signals in DRD4, DAT1 and 16 other genes

被引:418
作者
Brookes, K.
Xu, X.
Chen, W.
Zhou, K.
Neale, B.
Lowe, N.
Aneey, R.
Franke, B.
Gill, M.
Ebstein, R.
Buitelaar, J.
Sham, P.
Campbell, D.
Knight, J.
Andreou, P.
Altink, M.
Arnold, R.
Boer, F.
Buschgens, C.
Butler, L.
Christiansen, H.
Feldman, L.
Fleischman, K.
Fliers, E.
Howe-Forbes, R.
Goldfarb, A.
Heise, A.
Gabriels, I.
Korn-Lubetzki, I.
Marco, R.
Medad, S.
Minderaa, R.
Mulas, F.
Mueller, U.
Mulligan, A.
Rabin, K.
Rommelse, N.
Sethna, V.
Sorohan, J.
Uebel, H.
Psychogiou, L.
Weeks, A.
Barrett, R.
Craig, I.
Banaschewski, T.
Sonuga-Barke, E. J. S.
Eisenberg, J.
Kuntsi, J.
Manor, I.
McGuffin, P.
机构
[1] Inst Psychiat, MRC, Social Genet Dev & Psychiat Ctr, London SE5 8AF, England
[2] St James Hosp, Dept Psychiat, Trinity Ctr Hlth Sci, Dublin 8, Ireland
[3] Radboud Univ Nijmegen, Nijmegen Med Ctr, Nijmegen, Netherlands
[4] S Herzog Mem Hosp, Jerusalem, Israel
[5] Triversum, Alkmaar, Netherlands
[6] Amsterdam Med Ctr Bascule, Amsterdam, Netherlands
[7] Univ Essen Gesamthsch, Clin Child & Adolescent Psychiat, Essen, Germany
[8] Geha Mental Hlth Ctr, ADHD Clin, Petah Tiqwa, Israel
[9] Univ Gottingen, D-3400 Gottingen, Germany
[10] Univ Ghent VIB, Dept Expt Clin Hlth Psychol, B-9052 Ghent, Belgium
[11] Shaare Zedek Med Ctr, Jerusalem, Israel
[12] Univ Groningen, Ctr Child & Adolescence Psychiat, NL-9700 AB Groningen, Netherlands
[13] Univ Valencia, Dept Dev & Educ Psychol, E-46003 Valencia, Spain
[14] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland
[15] Vrije Univ Amsterdam, Amsterdam, Netherlands
[16] Univ Southampton, Sch Psychol, Southampton SO9 5NH, Hants, England
[17] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA
[18] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA
[19] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA
基金
英国医学研究理事会;
关键词
ADHD; association study; dopamine; noradrenaline; serotonin; candidate gene; linkage disequilibrium;
D O I
10.1038/sj.mp.4001869
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.
引用
收藏
页码:934 / 953
页数:20
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