CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
复制标题
DOI：
10.1016/j.xgen.2022.100167
复制
发表时间：
2022-08-10
期刊：
影响因子：
--
通讯作者：
Birney, Ewan
中科院分区：
文献类型：
--
作者：
Fitzgerald, Tomas;Birney, Ewan
拷贝数变异（CNV）已知会影响人类性状，在常见和罕见遗传疾病的研究中有着丰富的历史，尽管拷贝数变异被认为是一类重要的基因组变异，但基于拷贝数的全基因组关联研究（GWASs）在下一代测序（NGS）数据中的进展有限。在这里，我们提出了一种基于NGS数据的大规模拷贝数分析的新方法，产生稳健的拷贝数估计，并允许在发现模式下进行全基因组的拷贝数GWASs （CN-GWASs）。我们提供英国生物银行资源的详细分析和专门设计的软件包。我们使用这些方法对78个人类性状进行了CN-GWAS分析，发现了800多个可能对性状分布有重要影响的遗传关联。最后，我们比较了相同性状和样本中的CNV和SNP关联信号，定义了特定的CNV关联类别。基于新一代测序数据的大规模CNV关联检测为GA4GH标准下的CNV专门设计的GWAS框架SNP和CNV关联以及CNV标记SNP的研究巢拷贝数变异（CNV）全基因组关联研究（GWAS）测试将CNV引入到与广泛应用于SNP GWAS的框架相似的框架中。我们在英国生物银行（UK Biobank）的人类队列中获得了800多个外显子水平分辨率的新发现，为使用下一代测序数据进行进一步的CNV GWAS研究铺平了道路。
Copy number variation (CNV) is known to influence human traits, having a rich history of research into common and rare genetic disease, and although CNV is accepted as an important class of genomic variation, progress on copy-number-based genome-wide association studies (GWASs) from next-generation sequencing (NGS) data has been limited. Here we present a novel method for large-scale copy number analysis from NGS data generating robust copy number estimates and allowing copy number GWASs (CN-GWASs) to be performed genome-wide in discovery mode. We provide a detailed analysis in the UK Biobank resource and a specifically designed software package. We use these methods to perform CN-GWAS analysis across 78 human traits, discovering over 800 genetic associations that are likely to contribute strongly to trait distributions. Finally, we compare CNV and SNP association signals across the same traits and samples, defining specific CNV association classes. Novel copy number variation (CNV) associations in a large human cohort Large-scale CNV association testing from next-generation sequencing data Specifically designed GWAS framework for CNV operating under GA4GH standards Investigation of SNP and CNV associations and CNV tagging SNPs CNest copy number variation (CNV) genome-wide association study (GWAS) testing brings CNVs into a similar framework as those widely used in SNP GWAS. We made over 800 new discoveries in the UK Biobank human cohort at exon-level resolution, paving the way for further CNV GWAS studies using next-generation sequencing data.
登录
查看更多内容
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
9.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole