Statistical, population genetics and genetic epidemiolog

这个项目涉及统计遗传学问题，特别是在开发和评估绘制人类特征变异图谱的方法方面。我们一直在研究多基因座方法，这些方法提供了跨表型模型的更高的效率，以及关于随机交配假设的稳健性。我们开发了一种新的方法来对预测疾病易感性和药物不良反应等特征的遗传变异进行统计作图。这种方法是基于这样一种观察，即在一个遗传关联区，等位基因之间的相关程度(连锁不平衡，LD)在病例组和对照组之间可能不同。通过目测LD“色标”，可以比较不同样本之间LD的范围和模式。然而，这类小区所传达的图案受随机变化的影响，有必要对LD差异进行统计评估。构建“LD对比”测试的一个困难是，在存在遗传关联的情况下，与Hardy-Weinberg(随机交配)比例的偏差可能在基于表型的样本中表现出来。即使基础群体处于Hardy-Weinberg平衡，也可能发生偏离单倍型随机配对的情况。因此，单倍型阶段化的标准技术是不可靠的。LD对比法解决了这个问题。当高易感性与一对“阴阳单倍型”(即在许多SNP位点携带不同等位基因的单倍型)相关联时，该方法被发现特别有效。 柴田京子博士(研究员)一直致力于改进基于可能性的统计方法，以将单倍型和双倍型与连续性状相关联。柴田博士一直在应用她的方法来研究疼痛敏感性的遗传成分。

This project is concerned with statistical genetics problems, particularly in the area of developing and evaluating methods for mapping human trait variation. We have been investigating multi-locus approaches that provide increased efficiency across models of phenotype, and robustness with respect to the random mating assumption. We have developed a novel approach to statistical mapping of genetic variants predictive of traits such as disease susceptibility and adverse reactions to drugs. The approach is based on an observation that in a region of genetic association, the extent of correlation between alleles (linkage disequilibrium, LD) can be different between the case and the control groups. The extent and the pattern of LD can be compared between samples by a visual inspection of LD "color plots". However, patterns conveyed by such plots are subject to random variation, and a statistical assessment of the LD difference is necessary. A difficulty in constructing an "LD contrast" test is that the deviations from the Hardy-Weinberg (random mating) proportions are likely to manifest in phenotype-based samples in the presence of genetic association. The deviations from random pairing of haplotypes are likely to occur even if the underlying population is in Hardy-Weinberg equilibrium. Thus, standard techniques of phasing haplotypes are unreliable. The LD contrast method deals with this issue. The method is found especially efficient when high susceptibilities are linked to a pair of "yin yang haplotypes", i.e. haplotypes carrying different alleles at many SNP sites. Dr. Kyoko Shibata (Research Fellow) has been working in the direction of improving the likelihood-based statistical methods for association of haplotypes and diplotypes with continuous traits. Dr. Shibata has been applying her methods to study genetic components of pain sensitivity.