Case-control association testing in the presence of unknown relationships.
Case-control association testing in the presence of unknown relationships.
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DOI：
10.1002/gepi.20418
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发表时间：
2009-12
影响因子：
2.1
通讯作者：
Weir, Bruce S.
中科院分区：
文献类型：
--
作者：
Choi, Yoonha;Wijsman, Ellen M.;Weir, Bruce S.
全基因组关联研究在未被识别的隐性关联存在时会导致夸大的假阳性结果。已经提出了许多方法来测试标记物和疾病之间的关联，并对已知的基于谱系的关系进行校正。然而，在大多数病例对照研究中，关系通常是未知的，但设计是基于假设的情况下，至少祖先的相关性。在这里，我们专注于调整神秘的相关性时，样本的系谱是未知的，特别是在背景下的样本从孤立的人群中的神秘的相关性可能是有问题的。我们估计使用最大似然法的神秘相关性，并使用校正卡方检验估计的亲属关系系数进行测试的背景下，未知的神秘相关性。亲属关系系数的估计准确地描述了真正相关的人之间的相关性，但对不相关的对有偏见。所提出的测试大大减少了假阳性结果，产生了p值的均匀零分布。特别是在家系信息缺失的情况下，亲属关系系数的估计仍然可以用来修正个体间的非独立性。将校正检验应用于来自遗传分离株的真实的数据集，并创建接近均匀的p值分布。因此，所提出的检验校正了用未校正的检验获得的p值的非均匀分布，并说明了该方法在真实的数据上的优势。
Genome-wide association studies result in inflated false positive results when unrecognized cryptic relatedness exists. A number of methods have been proposed for testing association between markers and disease with a correction for known pedigree-based relationships. However, in most case-control studies, relationships are generally unknown, yet the design is predicated on the assumption of at least ancestral relatedness among cases. Here, we focus on adjusting cryptic relatedness when the genealogy of the sample is unknown, particularly in the context of samples from isolated populations where cryptic relatedness may be problematic. We estimate cryptic relatedness using maximum-likelihood methods and use a corrected chi-square test with estimated kinship coefficients for testing in the context of unknown cryptic relatedness. Estimated kinship coefficients characterize precisely the relatedness between truly related people, but are biased for unrelated pairs. The proposed test substantially reduces spurious positive results, producing a uniform null distribution of p-values. Especially with missing pedigree information, estimated kinship coefficients can still be used to correct non-independence among individuals. The corrected test was applied to real data sets from genetic isolates and created a distribution of p-value that was close to uniform. Thus the proposed test corrects the non-uniform distribution of p-values obtained with the uncorrected test and illustrates the advantage of the approach on real data.
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影响因子：
2.1
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
1.5
作者：
Ritland, K
通讯作者：
Ritland, K
影响因子：
9.8
作者：
Pritchard, JK;Rosenberg, NA
通讯作者：
Rosenberg, NA
DOI：
10.1111/j.2517-6161.1977.tb01600.x
发表时间：
1977-01-01
期刊：
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-METHODOLOGICAL
影响因子：
--
作者：
DEMPSTER, AP;LAIRD, NM;RUBIN, DB
通讯作者：
RUBIN, DB