Association of rare haplotypes on ULK4 and MAP4 genes with hypertension.
Association of rare haplotypes on ULK4 and MAP4 genes with hypertension.
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DOI：
10.1186/s12919-016-0057-2
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Biswas S
中科院分区：
文献类型：
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作者：
Datta AS;Zhang Y;Zhang L;Biswas S
早些时候，3号染色体上的ULK 4和MAP 4基因上的几种变体与高血压有关。作为自然的后续步骤，我们探索这些基因中单倍型的关联。我们考虑遗传分析工作室19个真实的无关个体的数据，并通过滑动窗口方法分析5个单核苷酸多态性的单倍型块。我们应用4种单倍型关联方法-单倍型评分、单倍型glm、单倍型关联和逻辑贝叶斯LASSO（LBL）-并进行比较，使用序列核关联检验（SKAT）及其变体。我们发现几个罕见的单倍型块相关联。为了了解假阳性的比例，我们还分析了改变个体病例对照状态后的数据。我们发现，LBL，不像其他方法，保持低的假阳性率在罕见的单倍型的存在。因此，我们得出结论，发现与LBL相关的单倍型更有可能是真阳性。SKAT及其变体在两个基因上均未发现显著性。
Several variants have been implicated earlier on ULK4 and MAP4 genes on chromosome 3 to be associated with hypertension. As a natural follow-up step, we explore association of haplotypes in those genes. We consider the Genetic Analysis Workshop 19 real data on unrelated individuals and analyze haplotype blocks of 5 single-nucleotide polymorphisms through a sliding window approach. We apply 4 haplotype association methods—haplo.score, haplo.glm, hapassoc, and logistic Bayesian LASSO (LBL)—and for comparison, sequence kernel association test (SKAT) and its variants. We find several rare haplotype blocks to be associated. To get an idea about the false-positive proportions, we also analyzed the data after permuting the case-control status of individuals. We found that LBL, unlike the other methods, maintains low false-positive rates in presence of rare haplotypes. Thus, we conclude that the haplotypes found to be associated by LBL are more likely to be true positive. SKAT and its variants did not find significance on either gene.