Original Research ARTICLE
Genetic variation in hyperpolarization-activated cyclic nucleotide-gated channels and its relationship with neuroticism, cognition, and risk of depression
- 1 Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK
- 2 Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK
- 3 Department of Psychiatry, Yale Medical School, New Haven, CT, USA
- 4 Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
- 5 Centre for Molecular Medicine, Ninewells Hospital and Medical School, Dundee, UK
- 6 College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- 7 Division of Psychology, University of Edinburgh, Edinburgh, UK
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by four genes (HCN1–4) and, through activation by cyclic AMP (cAMP), represent a point of convergence for several psychosis risk genes. On the basis of positive preliminary data, we sought to test whether genetic variation in HCN1–4 conferred risk of depression or cognitive impairment in the Generation Scotland: Scottish Family Health Study. HCN1, HCN2, HCN3, and HCN4 were genotyped for 43 haplotype-tagging SNPs and tested for association with DSM-IV depression, neuroticism, and a battery of cognitive tests assessing cognitive ability, memory, verbal fluency, and psychomotor performance. No association was found between any HCN channel gene SNP and risk of depression, neuroticism, or on any cognitive measure. The current study does not support a genetic role for HCN channels in conferring risk of depression or cognitive impairment in individuals from the Scottish population.
Keywords: stress, depression, HCN channel, genetics, association, cognition, neuroticism
Citation: Mcintosh AM, Simen AA, Evans KL, Hall J, MacIntyre DJ, Blackwood D, Morris AD, Smith BH, Dominiczak A, Porteous D, Deary IJ and Thomson PA (2012) Genetic variation in hyperpolarization-activated cyclic nucleotide-gated channels and its relationship with neuroticism, cognition, and risk of depression. Front. Gene. 3:116. doi: 10.3389/fgene.2012.00116
Received: 25 March 2012; Accepted: 05 June 2012;
Published online: 02 July 2012.
Edited by:Jenae Neiderhiser, The Pennsylvania State University, USA
Reviewed by:Jaime Derringer, University of Colorado, USA
Andrew McQuillin, University College London, UK
Copyright: © 2012 Mcintosh, Simen, Evans,Hall,MacIntyre, Blackwood,Morris, Smith, Dominiczak, Porteous, Deary and Thomson. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Andrew M. McIntosh, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Kennedy Tower, Edinburgh EH10 5HF, UK. e-mail: email@example.com