Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.
Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.
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DOI：
10.1002/gepi.22093
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发表时间：
2018-03
影响因子：
2.1
通讯作者：
Chatterjee N
中科院分区：
文献类型：
--
作者：
Song M;Wheeler W;Caporaso NE;Landi MT;Chatterjee N
全基因组关联研究（GWAS）现在通常基于各种强大的统计算法对未分型的SNP进行插补，用于在参考数据集上训练插补。已知使用插补SNP的预测等位基因计数作为剂量变量可产生遗传关联的有效评分检验。在本文中，我们研究了如何最好地处理插补的SNP在各种现代复杂的测试遗传协会纳入基因-环境相互作用。我们专注于病例对照关联研究，其中可以使用替代方法进行潜在逻辑回归模型的推断，这些方法依赖于基础人群中基因-环境独立性假设的不同程度。随着越来越大规模的GWAS正在通过财团的努力，它是最好的，只有总结级的信息共享研究，我们还描述了简单的机制，实现评分测试的基础上标准的荟萃分析的“一步”最大似然估计跨研究。在模拟研究和肺癌全基因组关联研究的数据集的方法的应用程序说明所提出的方法，以保持I型错误率的基本测试程序的能力。对于估算的SNPs的分析，类似于分型SNPs，在基因-环境独立性的假设下，回顾性方法可以导致对基因-环境相互作用建模的相当大的效率增益。方法通过CGEN R软件包提供给公众使用。
Genome-wide association studies (GWAS) are now routinely imputed for untyped SNPs based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score-tests based on standard meta-analysis of “one-step” maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from genome-wide association study of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package.
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DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
3.5
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
通讯作者：
Albanes D
影响因子：
2.1
作者：
Kraft, P;Cox, DG;De Vivo, I
通讯作者：
De Vivo, I
影响因子：
2.1
作者：
Mukherjee, Bhramar;Ahn, Jaeil;Chatterjee, Nilanjan
通讯作者：
Chatterjee, Nilanjan
影响因子：
5
作者：
Cornelis, Marilyn C.;Tchetgen, Eric J. Tchetgen;Kraft, Peter
通讯作者：
Kraft, Peter