Liang Sherri G, Sadovnick A Dessa, Remick Ronald A, Keck Paul E, McElroy Susan L, Kelsoe John R
Department of Psychiatry, University of California, San Diego and San Diego VA Healthcare System, La Jolla, California 92093, USA.
Psychiatr Genet. 2002 Dec;12(4):231-5. doi: 10.1097/00041444-200212000-00006.
Bipolar disorder is a major psychiatric disorder characterized by extreme mood states that alternate between mania and depression. Family, twin, and adoption studies indicate a genetic component to the disease, but the etiology is suspected to be complex, with multiple genes contributing to an increased susceptibility to the disorder. We have previously reported a genome scan in which a genome-wide maximum LOD score indicated evidence of linkage at the marker D22S278 at 22q13. This area is of particular interest since it is also implicated in schizophrenia, and thus may harbor a susceptibility gene common to both disorders. In our further efforts to fine map this region, we examined 10 microsatellite markers spanning an interval of 2.3 MB in a set of 142 parent-proband triads. Linkage disequilibrium to illness was tested using the Transmission Disequilibrium Test. Haplotypes were determined and marker-to-marker linkage disequilibrium across the region was examined. D22S281 and D22S685 yielded suggestive evidence of linkage disequilibrium to bipolar disorder (empirical values of 0.023 and 0.036, respectively), but a marker-to-marker analysis indicates that a higher density screen is needed to adequately analyze this region.
双相情感障碍是一种主要的精神疾病，其特征是在躁狂和抑郁之间交替出现的极端情绪状态。家族、双胞胎和收养研究表明该疾病存在遗传因素，但病因被怀疑很复杂，多个基因导致对该疾病的易感性增加。我们之前报道了一项全基因组扫描，其中全基因组最大LOD分数表明在22q13的标记D22S278处存在连锁证据。这个区域特别受关注，因为它也与精神分裂症有关，因此可能含有这两种疾病共有的易感基因。在我们进一步精细定位该区域的工作中，我们在一组142个亲代-先证者三联体中检查了跨越2.3兆碱基间隔的10个微卫星标记。使用传递不平衡检验来测试与疾病的连锁不平衡。确定了单倍型，并检查了该区域内标记与标记之间的连锁不平衡。D22S281和D22S685产生了与双相情感障碍连锁不平衡的提示性证据（经验值分别为0.023和0.036），但标记与标记分析表明需要更高密度的筛查才能充分分析该区域。
