title: Association of polymorphisms in HCN4 with mood disorders and obsessive compulsive disorder.
abstract: Hyperpolarization activated cyclic nucleotide-gated (HCN) potassium channels are implicated in the control of neuronal excitability and are expressed widely in the brain. HCN4 is expressed in brain regions relevant to mood and anxiety disorders including specific thalamic nuclei, the basolateral amygdala, and the midbrain dopamine system. We therefore examined the association of HCN4 with a group of mood and anxiety disorders. We genotyped nine tag SNPs in the HCN4 gene using Sequenom iPLEX Gold technology in 285 Caucasian patients with DSM-IV mood disorders and/or obsessive compulsive disorder and 384 Caucasian controls. HCN4 polymorphisms were analyzed using single marker and haplotype-based association methods. Three SNPs showed nominal association in our population (rs12905211, rs3859014, rs498005). SNP rs12905211 maintained significance after Bonferroni correction, with allele T and haplotype CTC overrepresented in cases. These findings suggest HCN4 as a genetic susceptibility factor for mood and anxiety disorders; however, these results will require replication using a larger sample.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kelmendi
authors.forename: Márcia
authors.initials: M
authors.lastname: Holsbach-Beltrame
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: Lori
authors.initials: L
authors.lastname: Hilt
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: George
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kitchen
authors.forename: Becky C
authors.initials: BC
authors.lastname: Carlyle
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
authors.forename: Vladimir
authors.initials: V
authors.lastname: Coric
authors.forename: Susan
authors.initials: S
authors.lastname: Nolen-Hoeksema
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Simen
mesh_terms: D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D009124:Muscle Proteins / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015221:Potassium Channels; D018570:Risk Assessment
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D005819:Genetic Markers; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels