Abstract
Genome-wide association (GWA) studies provide an unbiased approach to discovering the role of genetic determinants of disease across the human genome. The case–control design, the most frequently used GWA study design employed to date, compares allele frequencies in affected patients to those of unaffected controls. Several large-scale GWA studies have identified numerous risk variants for celiac disease (CD). However, due to their low marker density, the early GWA arrays failed to adequately capture much of the genetic variance associated with CD. The Immunochip, a custom Illumina Infinium high-density array containing 196,524 common and rare polymorphisms, was developed to allow deep replication and fine mapping of the previously established GWA significant loci identified in 12 major autoimmune and inflammatory diseases, including CD. It has the advantage of allowing uniform sets of genetic markers to be compared across all diseases. This chapter describes the methods used to perform Immunochip genotyping and the bioinformatics steps necessary for quality control and analysis of the resulting data.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
National Institutes of Health (2007) Policy for sharing of data obtained in NIH supported or conducted genome-wide association studies (GWAS). Federal Regist 72(166):49290–49297. http://www.grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html. Accessed on January 2015
Turner S, Armstrong LL, Bradford Y et al (2011) Quality control procedures for genome wide association studies. Curr Protoc Hum Genet. Chapter 1:Unit 1.19
Burton PR, Clayton DG, Cardon LR et al (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678
Van Heel DA, Franke L, Hunt KA et al (2007) A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 39:827–829
Hunt KA, Zhernakova A, Turner G et al (2008) Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 40:395–402
Dubois PCA, Trynka G, Franke L et al (2010) Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 42:295–302
Cortes A, Brown MA (2011) Promise and pitfalls of the Immunochip. Arthritis Res Ther 13:101
Trynka G, Hunt KA, Bockett NA et al (2011) Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet 43:1193–1201
Juran BD, Hirschfield GM, Invernizzi P et al (2012) Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants. Hum Mol Genet 21:5209–5221
Cooper JD, Simmonds MJ, Walker NM et al (2012) Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet 21:5202–5208
Green EK, Hamshere M, Forty L et al (2013) Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case–control sample. Mol Psychiatry 18:1302–1307
Coleman C, Quinn EM, Ryan AW, et al (2015) Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci. Eur J Hum Genet. doi:10.1038/ejhg.2015.87
Romanos J, Rosén A, Kumar V et al (2014) Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants. Gut 63:415–422
Acknowledgments
We would like to thank Dr. Anthony W. Ryan, Ms Valerie Trimble, and all who contributed samples for their help. This work was supported by Science Foundation Ireland (SFI) grant 09/IN.1/B2640 to R.M.M.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Coleman, C., Quinn, E.M., McManus, R. (2015). Quality Control Procedures for High-Throughput Genetic Association Studies. In: Ryan, A. (eds) Celiac Disease. Methods in Molecular Biology, vol 1326. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2839-2_17
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2839-2_17
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2838-5
Online ISBN: 978-1-4939-2839-2
eBook Packages: Springer Protocols