Center of Clinical Psychopharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, Via Ospedale 46, Cagliari, Italy.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1200-8. doi: 10.1002/ajmg.b.31092.
The discovery of the genetic factors implicated in the predisposition to complex diseases may greatly profit from genetic studies in isolated populations. In this perspective, we performed a genome-wide scan using 507 microsatellite markers, with an average interval size of 7.6 cM, on a sample of 88 nuclear families with at least two affected sibs with bipolar disorder recruited in the Sardinian population. An initial analysis yielded non-parametric linkage exceeding 3.4 with P-values <0.0003 at two adjacent markers, D1S206 and D1S435 in the 1p22-p21 chromosomal region. Moreover, positive linkage ranging between 2.0 and 3.0 was obtained for other loci in several cases in regions that have already been linked to predisposition to bipolar disorder, such as 5p15.33, 8q24.13, and 11q14.3. A subsequent analysis of the 1p22-p21 region using the same set of families and a dense panel of 20 new microsatellite markers, spaced at 1.2 cM on average, reinforced the finding of suggestive linkage for this region. Interestingly, NPL values above 2.1 and P-values <0.02 were obtained for a cluster of 10 markers comprising D1S435. Thus, this study suggests that the 1p22-p21 region may contain a new locus participating to the genetic susceptibility to bipolar disorder and reproduces positive linkage for several other loci already implicated in this pathology. Since the Sardinian population presents a peculiar genetic homogeneity, these results may pave the way to further studies for replication in this population contributing to the rapid discovery of the genetic factors predisposing to bipolar disorder.
复杂疾病易感性相关遗传因素的发现可能会极大地受益于对隔离人群的遗传研究。在此方面，我们在撒丁岛人群中对至少有两个双相障碍先证者的 88 个核心家系进行了全基因组扫描，使用了 507 个微卫星标记，平均间隔大小为 7.6cM。初步分析在 1p22-p21 染色体区域的两个相邻标记 D1S206 和 D1S435 上产生了超过 3.4 的非参数连锁，P 值<0.0003。此外，在多个病例中，在已经与双相障碍易感性相关的区域，如 5p15.33、8q24.13 和 11q14.3，获得了其他基因座的阳性连锁，其范围在 2.0 到 3.0 之间。使用相同的家系集和 20 个新的微卫星标记的密集面板（平均间隔为 1.2cM）对 1p22-p21 区域进行的后续分析，强化了该区域存在提示性连锁的发现。有趣的是，对于包含 D1S435 的 10 个标记簇，NPL 值超过 2.1，P 值<0.02。因此，本研究表明 1p22-p21 区域可能包含一个新的参与双相障碍遗传易感性的基因座，并且还对已经涉及该病理学的其他几个基因座产生了阳性连锁。由于撒丁岛人群具有独特的遗传同质性，这些结果可能为在该人群中进行进一步的复制研究铺平道路，有助于快速发现导致双相障碍的遗传因素。
