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We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a previously reported candidate region for PD. Three single nucleotide polymorphisms (rs887231, rs887230 and rs4795942) located upstream and within TMEM132E showed a nominal significant association with PD primarily in the Danish cohort. No nominal significant associations were observed between TMEM98 and PD. Our data indicate that TMEM132E might contribute moderately towards the risk of developing PD. [ABSTRACT FROM AUTHOR]

Panic disorder (PD) is a common psychiatric disease occurring more frequently in women than men. Multiple common and/or rare variants in the genome contribute to the complex etiology of the disorder. The neuropeptide cholecystokinin (CCK) and its receptors (the CCK system) have been suggested to be involved in the pathogenesis of PD.We examined the promoter, exon, and exon-intron boundaries of the genes encoding CCK and its receptors (CCKAR and CCKBR) for variations in 187 patients with PD and 277 screened control individuals. Up to 1342 additional healthy population controls were examined for some of the variations. One CCK gene intron variation was analyzed for alternative splicing using an exon-trapping assay.The promoter variant (-36C > T; rs1799923) and an intron 1 polymorphism (IVS1-7C > G; rs754635) in the CCK gene were found to protect against PD (P<0.05). The intron 1 variation did not seem to alter the splicing of the gene. None of the other variations found were associated with PD, but a 2-marker haplotype (rs1800855/rs1800857) in the CCKAR gene protected women against PD (P=0.004). In addition, we found two novel rare missense variations in the CCKBR gene (Lys329Asn and Pro446Leu) in two and one patient, respectively.The results suggest that the CCK system may play a role in the pathogenesis of PD, with susceptibility alleles both protecting and contributing to the disease. Both common and rare variants seem to be involved. The involvement of the CCK system may also contribute to the increased prevalence of PD in women. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in diacylglycerol kinase eta (DGKH) have recently been shown to be associated with bipolar disorder (BD). To replicate this finding, we carried out a gene-wide genotyping of 36 tagSNPs in DGKH and performed a population-based association study on two Scandinavian samples, with successful genotyping of 594 BD cases and 1421 healthy controls. We found no significant association after multiple-testing correction between any of these SNPs and BD in our sample. Thus, it is unlikely that these genetic variations confer susceptibility to BD in this large Scandinavian sample. [ABSTRACT FROM AUTHOR]

Objective: The intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene has been associated with rupture of intracranial aneurysms, but the effect of haplotypes within ACE has not been studied. This study investigated whether ACE haplotypes including the I/D polymorphism are associated with aneurysmal subarachnoid hemorrhage., Methods: The hypothesis was tested with a case-control design in 176 patients with aneurysmal subarachnoid hemorrhage and with 498 hospital controls. Through the pairwise tagging principle, single nucleotide polymorphisms (rs4291 A/T, rs4295 C/G, rs4305 C/T, rs4311 C/T, rs4331 T/C, rs4343 C/T) in the ACE gene were genotyped along with the I/D polymorphism. Haplotypes were estimated using the PHASE software., Results: Fifty-five haplotypes were identified with 3 of these having a frequency above 5%: ACCCCIT (41.6±0.4%), TGTTTDC (32.1±0.5%), and ACCTTDC (9.5±0.2%). No significant difference in distribution of alleles, genotypes, haplotypes, or haplotype pairs between the 2 populations was found. Specifically, we could not reproduce previously reported associations between the ACE I genotype and intracranial aneurysms. When subdivided into groups of aneurysm location, we found a trend toward an association between homozygotes of the ACCCCIT haplotype and middle cerebral artery aneurysms, odds ratio=2.9 (1.0 to 7.6), which however proved insignificant (P=0.22) after correction for multiple testing., Conclusion: In this Danish population, ACE haplotypes and the I/D polymorphism did not contribute significantly to the overall risk of intracranial aneurysm rupture. Larger studies are needed to delineate the association between ACE polymorphism and ruptured middle cerebral artery aneurysms.