Nwulia Evaristus A, Miao Kuangyi, Zandi Peter P, Mackinnon Dean F, DePaulo J Raymond, McInnis Melvin G
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bipolar Disord. 2007 Sep;9(6):580-8. doi: 10.1111/j.1399-5618.2007.00437.x.
Bipolar disorder (BD) II is characterized by recurrent hypomanic and depressive episodes and has been somewhat of a controversial diagnosis since its description in the 1970s. Clinical opinions notwithstanding, the biological validity of BD II was supported in a genetic study of 58 multiplex bipolar families wherein the statistical evidence for linkage derived from BD II sibling-pairs sharing marker alleles on chromosome 18q. The BD II phenotype alone has never been studied in a genome-wide scan analysis in the current or other bipolar family samples. We have performed genome-wide non-parametric analysis on 74 bipolar pedigrees using only the BD II phenotype as affection model.
This sample consists of the 65 pedigrees previously reported and 9 additional novel pedigrees that had BD II exclusively, as the affected phenotype. In the entire sample, there were 146 all possible relative-pairs. Analysis was performed using the non-parametric method in GENEHUNTER, with the 'ALL' option that computes linkage scores in all individuals in a pedigree simultaneously.
The current analyses supported the previous finding on chromosome 18q21. In addition a peak with a non-parametric LOD (NPL) of 2.07 occurred between D9S915 and D9S2157, located on 9q34. Analysis of the nine BD II families alone identified peaks on 9p13 and 9q33, with NPL scores of 3.20 and 2.09, respectively. There was no evidence at 18q21 in these nine families.
This suggests that there may be substantial differences in the etiology of BD in families that have BD II exclusively as the diagnosis.
双相情感障碍（BD）II型的特征为反复出现轻躁狂和抑郁发作，自20世纪70年代被描述以来，一直存在一定争议。尽管有临床观点，但在一项对58个多重双相情感障碍家族的遗传学研究中支持了BD II型的生物学有效性，该研究中连锁的统计学证据来自于在18号染色体q臂上共享标记等位基因的BD II型同胞对。仅BD II型表型从未在当前或其他双相情感障碍家族样本的全基因组扫描分析中进行过研究。我们仅以BD II型表型作为患病模型，对74个双相情感障碍家系进行了全基因组非参数分析。
该样本包括先前报道的65个家系和另外9个仅患有BD II型作为患病表型的新的家系。在整个样本中，有146对所有可能的亲属对。使用GENEHUNTER中的非参数方法进行分析，采用“ALL”选项，该选项可同时计算家系中所有个体的连锁分数。
当前分析支持先前在18号染色体q21区域的发现。此外，在位于9号染色体q34区域的D9S915和D9S2157之间出现了一个非参数LOD（NPL）为2.07的峰值。仅对这9个BD II型家族进行分析时，在9号染色体p13和9号染色体q33区域发现了峰值，NPL分数分别为3.20和2.09。在这9个家族的18号染色体q21区域未发现证据。
这表明仅以BD II型作为诊断的家族中，双相情感障碍的病因可能存在实质性差异。
