Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

• DOI: 10.1186/s13073-015-0211-x
• Publication Date: 2015-08-20T09:05:12Z
• Authors: Yun R. Li; Jessica van Setten; Shefali S. Verma; Yontao Lu; Michael V. Holmes; Hui Gao; Monkol Lek; Nikhil Nair; Hareesh Chandrupatla; Baoli Chang; Konrad J. Karczewski; Chanel Wong; Maede Mohebnasab; Eyas Mukhtar; Randy Phillips; Vinicius Tragante; Cuiping Hou; Laura Steel; Takesha Lee; James Garifallou; Toumy Guettouche; Hongzhi Cao; Weihua Guan; Aubree Himes; Jacob van Houten; Andrew Pasquier; Reina Yu; Elena Carrigan; Michael B. Miller; David Schladt; Abdullah Akdere; Ana Gonzalez; Kelsey M. Llyod; Daniel McGinn; Abhinav Gangasani; Zach Michaud; Abigail Colasacco; James Snyder; Kelly Thomas; Tiancheng Wang; Baolin Wu; Alhusain J. Alzah...; Amein K. Al-Ali; Fahad A. Al-Muhanna; Abdullah M. Al-Ru...; Samir Al-Mueilo; Dimitri S. Monos; Barbara Murphy; Kim M. Olthoff; Cisca Wijmenga; Teresa Webster; Malek Kamoun; Suganthi Balasubr...; Matthew B. Lanktree; William S. Oetting; Pablo Garcia-Pavia; Daniel G. MacArthur; Paul I W de Bakker; Hakon Hakonarson; Kelly A. Birdwell; Pamala A. Jacobson; Marylyn D. Ritchie; Folkert W. Asselb...; Ajay K. Israni; Abraham Shaked; Brendan J. Keating
• Keywords: Human genetics; Genome-wide Association Study

In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading allograft rejection are now becoming evident. We aimed create a unique genome-wide platform facilitate genomic research studies in transplant-related studies. designed genotyping tool based on the most recent human reference datasets, included customization for known potentially relevant metabolic pharmacological loci transplantation. describe here design implementation customized array, 'TxArray', comprising approximately 782,000 markers with tailored content deeper capture variants across HLA, KIR, pharmacogenomic, important To test concordance quality, we genotyped 85 HapMap samples including eight trios. show low Mendelian error rates high (average parent-parent-child heritability 0.997, 0.996). performed genotype imputation autosomal regions, masking directly SNPs assess accuracy report an >0.962 SNPs. demonstrate much higher natural killer cell immunoglobulin-like receptor (KIR) region versus comparable platforms. Overall, that quality coverage TxArray is very when compared other have comprehensive which enables accurate association testing ungenotyped SNPs, facilitating powerful cost-effective large-scale