Besides linkage analysis, many case-control design studies on candidate genes for anxiety pathogenesis have been performed. For panic disorder, a positive association was found for the serotonin receptors HTR1A (5q11.2-q13) and HTR2A (13q14-q21) [121, 122], COMT [123], the neuropeptide cholecystokinin (CCK; 3p22-p21.3) [124], the adenosine A2a receptor (ADORA2A; 22q11.23) [125], MAOA [126], the nuclear transcription factor cAMP-responsive element modulator (CREM; 10p11.21) [127], the peripheral benzodiazepine receptor (PBR or TSPO; 22q13.31) [128], glutamic acid decarboxylase 1 (GAD1; 2q31) [129], diazepam binding inhibitor (DBI; 2q12-q21) [130], calmodulin-dependent protein kinase kinase b (CaMKKb; 12q24.2) [131] and angiotensin-converting enzyme (ACE; 17q23.3) [132]. In addition, an association analysis of 90 SNPs located in 21 candidate genes revealed eight SNPs to be associated with panic disorder (located in the CCK, serotonin and dopamine systems), but all with a minor individual effect [133].
