Savage Jeanne E, McMichael Omari, Gorlin Eugenia I, Beadel Jessica R, Teachman Bethany, Vladimirov Vladimir I, Hettema John M, Roberson-Nay Roxann
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Biol Psychol. 2015 Jul;109:61-6. doi: 10.1016/j.biopsycho.2015.04.006. Epub 2015 Apr 22.
Few replicable genetic variants have been identified in the etiology of heritable anxiety disorders such as panic disorder. Endophenotypic measures that have reduced heterogeneity may provide more powerful targets for gene identification. We assessed hypersensitivity to carbon dioxide (a reliable endophenotype of panic and anxiety) in 174 Caucasian college students, who were genotyped on 26 polymorphic markers from 11 genes previously associated with panic/anxiety. Individual trajectories of respiratory and subjective anxiety response to carbon dioxide were measured and tested for association with these genetic markers. One marker in the acid-sensing ion channel 1 (ASIC1) gene, rs1108923, had a significant association with respiratory rate. No genes had a significant association with subjective anxiety response. Our findings support previously reported associations between ASIC1 and panic/anxiety, but not other genes previously associated with anxiety disorders. The use of endophenotypic markers is a promising avenue for gene identification in anxiety and other complex disorders.
在诸如惊恐障碍等遗传性焦虑症的病因中，几乎没有可复制的基因变异被识别出来。减少异质性的内表型测量方法可能为基因识别提供更有力的靶点。我们评估了174名白人大学生对二氧化碳的高敏反应（惊恐和焦虑的一种可靠内表型），这些学生针对先前与惊恐/焦虑相关的11个基因的26个多态性标记进行了基因分型。测量了对二氧化碳的呼吸和主观焦虑反应的个体轨迹，并测试其与这些基因标记的关联。酸敏感离子通道1（ASIC1）基因中的一个标记rs1108923与呼吸频率有显著关联。没有基因与主观焦虑反应有显著关联。我们的研究结果支持先前报道的ASIC1与惊恐/焦虑之间的关联，但不支持先前与焦虑症相关的其他基因。使用内表型标记是焦虑症和其他复杂疾病基因识别的一个有前景的途径。
