Vazza G, Bertolin C, Scudellaro E, Vettori A, Boaretto F, Rampinelli S, De Sanctis G, Perini G, Peruzzi P, Mostacciuolo M L
Department of Biology, University of Padova, Padova, Italy.
Mol Psychiatry. 2007 Jan;12(1):87-93. doi: 10.1038/sj.mp.4001895. Epub 2006 Sep 12.
Schizophrenia (SZ) and bipolar disorder (BPD) are two severe psychiatric diseases with a strong genetic component. In agreement with the 'continuum theory', which suggests an overlap between these disorders, the existence of genes that affect simultaneously susceptibility to SZ and BPD has been hypothesized. In this study we performed a 7.5 cM genome scan in a sample of 16 families affected by SZ and BPD, all originating from the same northeast Italian population. Using both parametric and non-parametric analyses we identified linkage peaks on four regions (1p, 1q, 4p and 15q), which were then subjected to a follow-up study with an increased marker density. The strongest linkage was obtained on chromosome 15q26 with a non-parametric linkage of 3.05 for marker D15S1014 (nominal P=0.00197). Interestingly, evidence for linkage with the same marker has been reported previously by an independent study performed on SZ and BPD families from Quebec. In this region, the putative susceptibility gene ST8SIA2 (also known as SIAT8B) was recently associated with SZ in a Japanese sample. However, our allele frequency analyses of the two single-nucleotide polymorphisms (SNPs) with putative functional outcome (rs3759916 and rs3759914) suggest that these polymorphisms are unlikely to be directly involved in SZ in our population. In conclusion, our results support the presence of a gene in 15q26 that influences the susceptibility to both SZ and BPD.
精神分裂症(SZ)和双相情感障碍(BPD)是两种具有很强遗传成分的严重精神疾病。与“连续体理论”一致,该理论表明这些疾病之间存在重叠,因此有人假设存在同时影响SZ和BPD易感性的基因。在本研究中,我们对来自意大利东北部同一人群的16个受SZ和BPD影响的家庭样本进行了7.5厘摩的基因组扫描。使用参数分析和非参数分析,我们在四个区域(1p、1q、4p和15q)确定了连锁峰,然后对这些区域进行了标记密度增加的后续研究。在15q26染色体上获得了最强的连锁,标记D15S1014的非参数连锁为3.05(名义P = 0.00197)。有趣的是,之前一项对来自魁北克的SZ和BPD家庭进行的独立研究报告了与同一标记的连锁证据。在该区域,推定的易感基因ST8SIA2(也称为SIAT8B)最近在一个日本样本中与SZ相关。然而,我们对两个具有推定功能结果的单核苷酸多态性(SNP)(rs3759916和rs3759914)的等位基因频率分析表明,这些多态性在我们的人群中不太可能直接参与SZ的发病。总之,我们的结果支持15q26中存在一个影响SZ和BPD易感性的基因。