Forstner Andreas J, Rambau Stefanie, Friedrich Nina, Ludwig Kerstin U, Böhmer Anne C, Mangold Elisabeth, Maaser Anna, Hess Timo, Kleiman Alexandra, Bittner Antje, Nöthen Markus M, Becker Jessica, Geiser Franziska, Schumacher Johannes, Conrad Rupert
aInstitute of Human Genetics bDepartment of Genomics, Life and Brain Center cClinic for Psychosomatic Medicine and Psychotherapy, University of Bonn, Bonn dDepartment of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany eDepartment of Psychiatry (UPK) fHuman Genomics Research Group, Department of Biomedicine, University of Basel gInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Psychiatr Genet. 2017 Jun;27(3):96-102. doi: 10.1097/YPG.0000000000000171.
Social anxiety disorder (SAD) is a common and heritable psychiatric disorder. However, genetic studies in SAD are rare and only a few candidate genes have been implicated so far. In the present study, we investigated whether single-nucleotide polymorphisms (SNPs) associated with other psychiatric disorders also contribute toward the development of SAD and followed up variants associated with SAD on the phenotypic level.
We genotyped a total of 24 SNPs in a German sample of 321 SAD patients and 804 controls. We carried out single-marker analyses as well as quantitative association analyses of SAD severity and harm avoidance.
None of the variants investigated showed an association with SAD in our case-control sample after Bonferroni correction. Two SNPs reached nominal significance (rs818702, P=0.032; rs140701, P=0.048). Of these, only rs140701 showed an association in the same allelic direction as reported previously. This SNP is located within the serotonin transporter gene SLC6A4, which is the primary target of selective-serotonin reuptake inhibitors used for the treatment of depressive and anxiety disorders. The quantitative association analysis of all cases with available data on symptom severity showed four SNPs with a nominal significant association. Among these SNPs, rs10994359 showed the strongest association (P=0.001) and was located near the ANK3 gene. In addition, rs10994359 was nominally associated with harm avoidance scores (P=0.001).
Our results provide further evidence for an involvement of the serotonin transporter gene SLC6A4 in the etiology of anxiety-related traits. Furthermore, our study implicates that genetic variation at the genome-wide associated bipolar disorder locus ANK3 might influence anxiety-related personality traits.
社交焦虑障碍（SAD）是一种常见的遗传性精神疾病。然而，SAD的遗传学研究较少，目前仅有少数候选基因被涉及。在本研究中，我们调查了与其他精神疾病相关的单核苷酸多态性（SNP）是否也与SAD的发生有关，并在表型水平上对与SAD相关的变异进行了随访。
我们对321例SAD患者和804例对照的德国样本中的24个SNP进行了基因分型。我们进行了单标记分析以及SAD严重程度和避免伤害的定量关联分析。
在经Bonferroni校正后的病例对照样本中，所研究的变异均未显示与SAD相关。两个SNP达到名义显著性（rs818702，P = 0.032；rs140701，P = 0.048）。其中，只有rs140701显示出与先前报道相同的等位基因方向的关联。该SNP位于血清素转运体基因SLC6A4内，该基因是用于治疗抑郁和焦虑症的选择性血清素再摄取抑制剂的主要靶点。对所有有症状严重程度可用数据的病例进行的定量关联分析显示，有4个SNP具有名义上的显著关联。在这些SNP中，rs10994359显示出最强的关联（P = 0.001），且位于ANK3基因附近。此外，rs10994359与避免伤害评分名义上相关（P = 0.001）。
我们的结果为血清素转运体基因SLC6A4参与焦虑相关性状的病因提供了进一步证据。此外，我们的研究表明全基因组关联双相情感障碍位点ANK3处的遗传变异可能影响焦虑相关的人格特质。
