We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.

中文翻译：

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拉丁美洲谱系中双相情感障碍易感基因座的精细图扫描。

我们先前在拉丁美洲人队列的全基因组非参数连锁筛选中，在8q24、14q32和2q12-14上确定了躁郁症（BD）易感基因座。现在，我们使用其他SNP的密集图进行精细定位分析，以识别这些区域内的BD易感基因。对来自美国，墨西哥，哥斯达黎加和危地马拉的416个拉丁裔谱系的198个拉丁裔谱系个体（880个BD I型或分裂亲和型，双极型880个个体）进行了基因型分型，并提供了3,074个SNP以提供密集的覆盖8q24（11.5 cM），14q32（7.5 cM）和2q12-14（6.5 cM）染色体基因座 使用LAMP软件在存在连锁的情况下进行单标记关联测试。顶部连锁峰（rs7834818; LOD = 5.08，p = 3.30E-5）和相关的单个标记（rs2280915，p = 2.70E-12）位于8q24的FBXO32内。在2号染色体上，顶部连锁峰（rs6750326; LOD = 5.06，p = 3.50E-5）和相关的单个标记（rs11887088，p = 2.90E-6）位于ACTR3和DPP10附近的基因内区域。染色体14q32周围区域的其他标记均未达到连锁或缔合的显着性水平。我们在2q12-q14上鉴定了6个SNP，在8q24上在FBXO32中鉴定了一个SNP，它们与该拉丁裔队列中的BD显着相关。