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Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder
Author(s) -
Comings David E,
GadeAndavolu Radhika,
Gonzalez Nancy,
Wu Shijuan,
Muhleman Donn,
Blake Hezekiah,
Chiu F,
Wang E,
Farwell K,
Darakjy S,
Baker R,
Dietz George,
Saucier Gerard,
MacMurray James P
Publication year - 2000
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2000.580106.x
Subject(s) - gene , candidate gene , attention deficit hyperactivity disorder , genetics , medicine , biology , endocrinology , conduct disorder , psychology , psychiatry
In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178–196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation – cholinergic, nicotinic, alpha 4 receptor ( CHNRA4 ) , adenosine A2A receptor ( ADOA2A ) , nitric oxide synthase ( NOS3 ) , NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P‐450), ESR1, and INS (p=0.005). This is consistent with our prior studies indicating a role of the androgen receptor ( AR ) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.