Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
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DOI：
10.1534/genetics.115.178905
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发表时间：
2015-08-01
期刊：
影响因子：
3.3
通讯作者：
Risch, Neil
中科院分区：
文献类型：
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作者：
Kvale, Mark N.;Hesselson, Stephanie;Risch, Neil
Kaiser Permanente（KP）基因、环境和健康研究计划（RPGEH）与加利福尼亚大学旧金山分校（University of California San弗朗西斯科）合作，对构成成人健康和衰老遗传流行病学研究（GERA）队列的> 100，000名受试者进行了全基因组基因分型。该项目产生了超过700亿个基因型，代表了Affytechnology Axiom基因分型解决方案的首次大规模使用。由于基因分型在短短14个月内完成，因此为实验检测质量控制和最终优化分析创建近实时分析管道至关重要。由于队列的多种族性质，采用了四种不同的种族特异性阵列来提高全基因组覆盖率。所有测定均在从唾液样品中提取的DNA上进行。为了提高样本识别率并显著增加基因型一致性，我们将队列划分为具有相似测定背景的不相交板包。使用严格的QC标准，在109，837份分析样本中，总体基因分型成功率为103，067份（93.8%），四种不同阵列的范围为92.1-95.4%。类似地，SNP基因分型成功率在四个阵列中的范围为98.1%至99.4%，变化主要取决于在特定阵列上包括多少SNP作为单拷贝与双拷贝。在该队列中创建的高质量和大规模的基因型数据，以及来自参与者KP电子健康记录的全面纵向数据，将使广泛的高功率全基因组关联研究成为可能。
The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California-San Francisco, undertook genome-wide genotyping of >100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The project, which generated >70 billion genotypes, represents the first large-scale use of the Affymetrix Axiom Genotyping Solution. Because genotyping took place over a short 14-month period, creating a near-real-time analysis pipeline for experimental assay quality control and final optimized analyses was critical. Because of the multi-ethnic nature of the cohort, four different ethnic-specific arrays were employed to enhance genome-wide coverage. All assays were performed on DNA extracted from saliva samples. To improve sample call rates and significantly increase genotype concordance, we partitioned the cohort into disjoint packages of plates with similar assay contexts. Using strict QC criteria, the overall genotyping success rate was 103,067 of 109,837 samples assayed (93.8%), with a range of 92.1-95.4% for the four different arrays. Similarly, the SNP genotyping success rate ranged from 98.1 to 99.4% across the four arrays, the variation depending mostly on how many SNPs were included as single copy vs. double copy on a particular array. The high quality and large scale of genotype data created on this cohort, in conjunction with comprehensive longitudinal data from the KP electronic health records of participants, will enable a broad range of highly powered genome-wide association studies on a diversity of traits and conditions.