Multipoint linkage disequilibrium mapping approach: incorporating evidence of linkage and linkage disequilibrium from unlinked region.
Multipoint linkage disequilibrium mapping approach: incorporating evidence of linkage and linkage disequilibrium from unlinked region.
复制标题
多点连锁不平衡作图方法：合并来自未连锁区域的连锁和连锁不平衡的证据。
DOI：
10.1002/gepi.10241
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发表时间：
2003
影响因子：
2.1
通讯作者：
Beaty,TerriH
中科院分区：
文献类型：
--
作者：
Hsu,Fang-Chi;Liang,Kung-Yee;Beaty,TerriH
复杂疾病的基因定位仍然是遗传学研究中的一个挑战。在家系研究中，单位点方法一次检测一个连锁和连锁不平衡（LD）可能无法有效地捕捉多个致病基因之间的假设相互作用。我们提出了一个多点LD的方法来评估证据的连锁和LD在一个有针对性的染色体区域，将证据从一个未连锁的区域使用的情况下，父母三人组设计。父亲和母亲的优先传输统计定义在梁等。（[2001] Am. J. Genet. 68：937-950）是这种方法的主要统计数据。我们的广义估计方程（GEE）方法建立在一个模型上，使用预期的优惠传输统计从目标区域的条件下，从未连接的区域相同的统计。主要的假设是，在目标区域和非连锁区域中不存在多于一个的性状位点。可以计算未观察到的性状基因座的图位及其置信区间。最后，我们将这种方法应用于来自哮喘遗传学合作研究（CSGA）的非裔美国人家庭。以前的分析使用这种GEE方法开发的梁等人。（[2001] Am. J. Genet. 68：937-950）提出了在11号染色体上的连锁和LD的强有力证据，但在8号染色体上仅有边缘证据。当以11号染色体上的标记D11 S937为条件时，8号染色体上的单独性状基因座估计为Δ τ2 1/4 11.67 cM，95%置信区间为（8.75，14.59），并且检验统计量显示连锁和LD的显著证据（P值1/4 0. 0198）在该区域的染色体8。Genet Epidemiol 25：1-13，2003. & 2003 Wiley-Liss，Inc.
Gene mapping for complex diseases is still a challenge in genetic studies. For family-based studies, the single-locus methods for detecting linkage and linkage disequilibrium (LD) one at a time may not capture the assumed interaction between multiple causal genes efficiently. We propose a multipoint LD approach for assessing the evidence of linkage and LD in a targeted chromosomal region by incorporating evidence from an unlinked region using the case-parent trio design. The paternal and maternal preferential transmission statistics defined in Liang et al.([2001] Am. J. Hum. Genet. 68: 937–950) are the primary statistics for this approach. Our generalized estimating equation (GEE) method builds on a model using the expected preferential transmission statistic from the targeted region conditional on this same statistic from the unlinked region. The major assumption is that there is no more than one trait locus in both the targeted region and unlinked region. The map position of an unobserved trait locus and its confidence interval can be calculated. Finally, we apply this approach to the African-American families drawn from the Collaborative Study on the Genetics of Asthma (CSGA). Previous analysis using this GEE approach developed by Liang et al.([2001] Am. J. Hum. Genet. 68: 937–950) suggested strong evidence of linkage and LD on chromosome 11, but only marginal evidence on chromosome 8. While conditioning on marker D11S937 on chromosome 11, a separate trait locus on chromosome 8 was estimated at ˆτ2 ¼ 11.67 cM, with a 95% confidence interval of (8.75, 14.59), and the test statistic shows significant evidence of linkage and LD (P-value¼0. 0198) in this region of chromosome 8. Genet Epidemiol 25: 1–13, 2003. & 2003 Wiley-Liss, Inc.