GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes
GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes
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DOI：
10.1016/j.ajhg.2016.07.020
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发表时间：
2016-10-06
影响因子：
9.8
通讯作者：
Nivard, Michel G.
中科院分区：
文献类型：
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作者：
Nieuwboer, Harold A.;Pool, Rene;Nivard, Michel G.
在这里，我们提出了一种全基因组推断研究（GWIS）的方法，它提供了一个近似的全基因组关联研究（GWAS）汇总统计量的变量，这是一个功能的表型，GWAS汇总统计量，表型均值和协方差。可以执行GWIS，而不管功能所依赖的表型的GWAS之间的样本重叠。由于GWIS提供了每个SNP的关联估计及其标准误差，因此GWIS可以形成多基因风险评分、LD评分回归、孟德尔随机化研究、生物注释和其他分析的基础。GWIS也可用于提高GWAS荟萃分析的功效，其中队列未测量功能中的所有组成表型。我们通过在不同情况下进行幂模拟和I型误差模拟来证明BMI GWIS的准确性，并且我们通过基于体重GWAS和身高GWAS重建体重指数（BMI）GWAS来应用GWIS。此外，我们应用GWIS进一步了解双相情感障碍和精神分裂症的潜在遗传结构及其与教育程度的关系。我们的分析表明，以前报道的精神分裂症和教育程度之间的遗传相关性可能是由观察到的精神分裂症和双相情感障碍之间的遗传相关性和以前报道的双相情感障碍和教育程度之间的遗传相关性。
Here we present a method of genome-wide inferred study (GWIS) that provides an approximation of genome-wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means, and covariances are available. A GWIS can be performed regardless of sample overlap between the GWAS of the phenotypes on which the function depends. Because a GWIS provides association estimates and their standard errors for each SNP, a GWIS can form the basis for polygenic risk scoring, LD score regression, Mendelian randomization studies, biological annotation, and other analyses. GWISs can also be used to boost power of a GWAS meta-analysis where cohorts have not measured all constituent phenotypes in the function. We demonstrate the accuracy of a BMI GWIS by performing power simulations and type I error simulations under varying circumstances, and we apply a GWIS by reconstructing a body mass index (BMI) GWAS based on a weight GWAS and a height GWAS. Furthermore, we apply a GWIS to further our understanding of the underlying genetic structure of bipolar disorder and schizophrenia and their relation to educational attainment. Our analyses suggest that the previously reported genetic correlation between schizophrenia and educational attainment is probably induced by the observed genetic correlation between schizophrenia and bipolar disorder and the previously reported genetic correlation between bipolar disorder and educational attainment.