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The interaction between serotonin receptor 2A and catechol-O-methyltransferase gene polymorphisms is associated with the novelty-seeking subscale impulsiveness

Salo, Johannaa; Pulkki-Råback, Lauraa b; Hintsanen, Mirkaa; Lehtimäki, Terhoc d; Keltikangas-Järvinen, Liisaa

doi: 10.1097/YPG.0b013e32833a212f
Original Articles

Objective Novelty seeking is a trait that has been consistently associated with problem behaviours. There is evidence for heritability of novelty seeking, but the molecular genetic basis of the trait is still widely unclear.

Methods The interaction between polymorphisms of catechol-O-methyltransferase (COMT) and serotonin receptor 2A genes was examined in relation to novelty seeking and its different subscales in healthy Finnish adults. A subsample of 1214 participants derived from a population-based sample was genotyped for the COMT Val158Met (rs4680) and HTR2A T102C (rs6313) genes. Novelty seeking was measured twice, with a 4-year interval, using Cloninger's Temperament and Character Inventory.

Results The interaction between COMT Val158Met and HTR2A T102C polymorphisms was found to be associated with subscale impulsiveness. T/T carriers of HTR2A T102C polymorphism, that also had Met/Met genotype of COMT Val158Met single nucleotide polymorphism, scored significantly higher on impulsiveness than Val allele carriers (P=0.005).

Conclusion Our results suggest that the interaction between dopaminergic and serotonergic genes might underlie impulsiveness. Together with earlier research our results also stress the importance of considering novelty seeking as a heterogeneous trait with its subscales having different genetic backgrounds.

aDepartment of Psychology, University of Helsinki

bFinnish Institute of Occupational Health, Helsinki

cLaboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital

dMedical School, University of Tampere, Tampere, Finland

Correspondence to Liisa Keltikangas-Järvinen, PhD, Department of Psychology, University of Helsinki, PO Box 9, FIN-00014 Helsinki, Finland

Tel: +358 9 191 29500; fax: +358 9 191 29521;


Received 11 May 2009 Revised 18 December 2009 Accepted 3 February 2010

© 2010 Lippincott Williams & Wilkins, Inc.