Tmem132d: a novel biomarker for anxiety disorders

Clinical data from a whole genome study of two independent case-control samples suggest an association of a SNP in intron three of the human gene TMEM132D and panic disorder. Moreover, there seems to be an association between some SNPs in this gene and the severity of anxiety in patients with panic disorder and patients with unipolar depression. Supporting evidence was recently obtained from our mouse model. CD1 mice were selectively bred for extremes in anxiety-related behavior. In a pilot sequencing study of high (HAB) versus low (LAB) anxiety-related behavior mice, seven single-nucleotide polymorphisms (SNPs) could be identified and validated using a Sequenom SNP genotyping assay in 16 HAB and 15 LAB animals. Additional evidence delivered by a gene expression microarray analysis suggested differenzial expression of Tmem132d in the cingulate cortex that could be validated using quantitative PCR. Finally, a highly significant association of the HAB-typical allele for Tmem132d and increased anxiety-related behavior – as reflected by the elevated-plus maze test – could be reported in a freely segregation F2 panel of HABxLAB intercross mice, converging with the data obtained from patients suffering from panic disorder. In the light of these data we suggest to consider TMEM132D as a biomarker for anxiety disorders.