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A high density linkage disequilibrium mapping in 14 noradrenergic genes: evidence of association between SLC6A2, ADRA1B and ADHD.
MedLine Citation:
PMID:  23052569     Owner:  NLM     Status:  Publisher    
Pharmacological evidence suggests the importance of noradrenergic and other monoaminergic neurotransmitters in the aetiology and treatment of attention deficit hyperactivity disorder (ADHD). Until recently, the genes of the noradrenergic pathway were not intensively investigated in ADHD compared to dopaminergic and serotonergic candidates. In this study, 91 SNP markers of 14 noradrenergic genes (an average density of one SNP per 4.5 kbp) were examined in ADHD samples from Ireland and Australia. Although suggestive evidence of association (nominal p ≤ 0.05) with the genes SLC6A2, ADRA1A, ADRA1B and ADRA2B was observed, none remained significant after permutation adjustments. In contrast, haplotype analyses demonstrated a significant association between ADHD and a SLC6A2 haplotype comprising the markers rs36009, rs1800887, rs8049681, rs2242447 and rs9930182 (χ(2) = 9.39, p-corrected = 0.019, OR = 1.51). A rare ADRA1B haplotype made of six SNPs (rs2030373, rs6884105, rs756275, rs6892282, rs6888306 and rs13162302) was also associated (χ(2) = 7.79, p-corrected = 0.042 OR = 2.74) with the disorder. These findings provide evidence of a contribution of the noradrenaline system to the genetic aetiology of ADHD. The observed haplotype association signals may be driven by as yet unidentified functional risk variants in or around the associated regions. Functional genomic analysis is warranted to determine the biological mechanism of the observed association.
Ziarih Hawi; Natasha Matthews; Edwina Barry; Aiveen Kirley; Joseph Wagner; Robyn H Wallace; Helen S Heussler; Alasdair Vance; Michael Gill; Mark A Bellgrove
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-29
Journal Detail:
Title:  Psychopharmacology     Volume:  -     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Queensland Brain Institute and School of Psychology, The University of Queensland, Brisbane, Queensland, Australia,
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