Exome- and whole-genome sequencing is becoming increasingly affordable and allows for detection and genotyping of rare variants in the human genome. Yet, genotyping arrays remain a cost-effective approach when investigating genetic polymorphisms previously identified in large populations. A limitation of using arrays to genotype rare variants is the difficulty that automated clustering algorithms have to accurately detect and assign accurate genotype calls. Large sample sizes increase the number of occurrences of rare variants and, therefore, should facilitate automated clustering and genotyping. Therefore, participating studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium consented to have their Illumina Infinium HumanExome BeadChip v1.0 intensity data analyzed collectively (n=62,266) in order to increase the accuracy of rare variant genotype calls. The resulting publication details our approach, and supplementary information presented in the manuscript are available for download below.
Grove ML, Yu B, Cochran BJ, Haritunians T, Bis JC, Taylor KD, Hansen M, Borecki I, Cupples LA, Fornage M, Gudnason V, Harris T, Katherisan S, Kraaij R, Launer LJ, Levy D, Liu Y, Mosley T, Peloso GM, Psaty BM, Rich SS, Rivadeneira F, Siscovick DS, Smith AV, Uitterlinden A, van Duijn CM, Wilson JG, O’Donnell CJ, Rotter JI, Boerwinkle E. Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium. PLoS ONE 8(7): e68095.