Department of Psychiatry, University of California, San Diego, CA, USA.
Bipolar Disord. 2012 Feb;14(1):71-9. doi: 10.1111/j.1399-5618.2011.00970.x.
We have previously reported the results of a linkage analysis of bipolar disorder in an initial set of 20 pedigrees ascertained through collaboration among three sites. We now report the results of our genome-wide linkage analysis in an independent sample of 34 pedigrees segregating bipolar disorder.
Families were ascertained through a bipolar I or II disorder proband for the presence of bipolar I disorder, bipolar II disorder, or recurrent major depression in at least two other family members. A total of 440 markers at an average spacing of 8 cM were genotyped in 229 family members using fluorescent methods.
Initial nonparametric analyses of chromosomes 6 and 17 provided evidence for a modest replication of linkage to these chromosomes previously reported in other studies. Additional analyses using multipoint parametric methods provided further evidence to support the 6q25 region with a heterogeneity logarithm of odds score of 3.28. Evidence from two-point parametric analyses also provides a modest replication of our previous findings of linkage to the 23 cM region of chromosome 22q13 in our original University of California, San Diego sample of 20 families and 57 families from the National Institute of Mental Health bipolar disorder sample.
Our results suggest replication of some reported linkage peaks, such as 6q25 and 17p12; however, other peaks from our own previous study, such as 5p15, 13q32, and 22q13, were either not replicated or were only modestly replicated in these analyses.
我们之前报道了通过三个合作站点确定的 20 个家系的双相情感障碍连锁分析的结果。我们现在报告在分离双相情感障碍的 34 个独立家系中进行的全基因组连锁分析的结果。
通过双相 I 或 II 障碍的先证者来确定家族，其家族成员中至少有两名患有双相 I 障碍、双相 II 障碍或复发性重度抑郁症。使用荧光方法在 229 名家庭成员中对 440 个平均间距为 8cM 的标记进行基因分型。
对染色体 6 和 17 的初始非参数分析提供了证据，证明了与先前在其他研究中报告的这些染色体的适度连锁复制。使用多点参数方法的其他分析进一步支持了 6q25 区域，其异质性对数优势评分达到 3.28。两点参数分析的证据也适度复制了我们之前在加利福尼亚大学圣地亚哥分校的 20 个家系和国家心理健康研究所的双相情感障碍样本的 57 个家系中发现的与染色体 22q13 的 23cM 区域的连锁。
我们的结果表明，一些已报道的连锁峰，如 6q25 和 17p12，得到了复制；然而，我们之前研究中的其他峰，如 5p15、13q32 和 22q13，要么没有得到复制，要么在这些分析中仅得到适度复制。
