Human Molecular Genetics Advance Access published online on June 14, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl152
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1 Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai 200030, China; Institutefor Nutritional sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
* To whom correspondence should be addressed. Molecular genetic investigations of Attention-Deficit Hyperactivity Disorder (ADHD) have found associations with a variable number of tandem repeat (VNTR) situated in the 3' untranslated region of DAT1, a VNTR in exon 3 of DRD4 and a microsatellite polymorphism located at 18.5 kb from the 5' end of DRD5. A number of independent studies have attempted to replicate these findings but the results have been mixed, possibly reflecting inadequate statistical power and the use of different populations and methodologies. In an attempt to clarify this inconsistency we have combined all the published studies of European and Asian populations up to October 2005 in a meta-analysis to give a comprehensive picture of the role of the three dopamine-related genes using multiple research methods and models. The DRD4 7-repeat (OR = 1.34, 95% C.I. 1.23 - 1.45, p = 2 x 10-12) and 5-repeat (OR = 1.68, 95% C.I. 1.17 - 2.41, p = 0.005) alleles as well as the DRD5 148-bp allele (OR = 1.34, 95% C.I. 1.21 - 1.49, p = 8 x 10-8) confer increased risk of ADHD, while the DRD4 4-repeat (OR = 0.90, 95% C.I. 0.84 - 0.97, p = 0.004) and DRD5 136-bp (OR = 0.57, 95% C.I. 0.34 - 0.96, p = 0.022) alleles have protective effects. In contrast we found no compelling evidence for association with the 480-bp allele of DAT (OR = 1.04, 95% C.I. 0.98 - 1.11, p = 0.20). No significant publication bias was detected in current studies. In conclusion, there is a statistically significant association between ADHD and dopamine system genes, especially DRD4 and DRD5. These findings strongly implicate the involvement of brain dopamine systems in the pathogenesis of ADHD.
Received April 5, 2006
Revised June 7, 2006
Accepted June 7, 2006
Article
Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD)
Dawei Li 1,
Pak C. Sham 2,
Michael J Owen 3,
and
Lin He 4 *
2 SGDP Centre, Institute of Psychiatry, King's College London, UK; Genome Research Center, The University of Hong Kong, Hong Kong SAR, China
3 Department of Psychological Medicine, Wales College of Medicine, Biology, Life & Health Science, Cardiff University, Cardiff, UK
4 Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China; or Shanghai Jiaotong University, Bio-X Center, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, People's Republic of China; NHGG Bio-X Center, Shanghai Jiaotong University, Shanghai 200030, China
Lin He, E-mail: helinhelin{at}gmail.com
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