Thorgeirsson Thorgeir E, Oskarsson Högni, Desnica Natasa, Kostic Jelena Pop, Stefansson Jon G, Kolbeinsson Halldor, Lindal Eirikur, Gagunashvili Nikolai, Frigge Michael L, Kong Augustine, Stefansson Kari, Gulcher Jeffrey R
deCode Genetics, Reykjavík, Iceland.
Am J Hum Genet. 2003 May;72(5):1221-30. doi: 10.1086/375141. Epub 2003 Apr 4.
The results of a genomewide scan for genes conferring susceptibility to anxiety disorders in the Icelandic population are described. The aim of the study was to locate genes that predispose to anxiety by utilizing the extensive genealogical records and the relative homogeneity of the Icelandic population. Participants were recruited in two stages: (1) Initial case-identification by a population screening for anxiety disorders, using the Stamm Screening Questionnaire, was followed by aggregation into extended families, with the help of our genealogy database; and (2) those who fulfilled the diagnostic and family aggregation criteria underwent a more detailed diagnostic workup based on the Composite International Diagnostic Interview. Screening for anxiety in close relatives also identified additional affected members within the families. After genotyping was performed with 976 microsatellite markers, affected-only linkage analysis was done, and allele-sharing LOD scores were calculated using the program Allegro. Linkage analysis of 25 extended families, in each of which at least one affected individual had panic disorder (PD), resulted in a LOD score of 4.18 at D9S271, on chromosome 9q31. The intermarker distance was 4.4 cM on average, whereas it was 1.5 cM in the linked region as additional markers were added to increase the information content. The linkage results may be relevant not only to PD but also to anxiety in general, since our linkage study included patients with other forms of anxiety.
本文描述了一项针对冰岛人群中焦虑症易感性基因进行全基因组扫描的结果。该研究的目的是通过利用冰岛人群广泛的系谱记录和相对同质性来定位易患焦虑症的基因。研究对象分两个阶段招募：（1）首先通过使用施塔姆筛查问卷对焦虑症进行人群筛查来初步识别病例，然后借助我们的系谱数据库将其汇总到大家庭中；（2）那些符合诊断和家族聚集标准的人根据综合国际诊断访谈进行更详细的诊断检查。对近亲进行焦虑症筛查也在家庭中发现了其他受影响成员。在用976个微卫星标记进行基因分型后，进行了仅患病例的连锁分析，并使用Allegro程序计算等位基因共享LOD分数。对25个大家庭进行连锁分析，每个大家庭中至少有一名受影响个体患有惊恐障碍（PD），在9号染色体9q31的D9S271处获得LOD分数为4.18。标记间平均距离为4.4厘摩，而在连锁区域中为1.5厘摩，因为添加了额外的标记以增加信息含量。该连锁结果可能不仅与惊恐障碍有关，而且与一般焦虑症有关，因为我们的连锁研究包括了患有其他形式焦虑症的患者。
