Abstract
Genome-wide association study (GWAS) is a powerful study design to identify genetic variants of a trait and, in particular, detect the association between common single-nucleotide polymorphisms (SNPs) and common human diseases such as heart disease, inflammatory bowel disease, type 2 diabetes, and psychiatric disorders. The standard strategy of population-based case-control studies for GWAS is illustrated in this chapter. We provide an overview of the concepts underlying GWAS, as well as provide guidelines for statistical methods performed in GWAS.
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References
Skol AD, Scott LJ, Abecasis GR, Boehnke M (2007) Optimal designs for two-stage genome-wide association studies. Genet Epidemiol 31(7):776–788. https://doi.org/10.1002/gepi.20240
Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24. https://doi.org/10.1016/j.ajhg.2011.11.029
Haldar T, Ghosh S (2011) Power comparison between population-based case-control studies and family-based transmission-disequilibrium tests: an empirical study. Indian J Hum Genet 17(Suppl 1):S27–S31. https://doi.org/10.4103/0971-6866.80355
Satagopan JM (2004) Two-stage designs for gene-disease association studies with sample size constraints. Biometrics 60(3):589–597
Kronenberg F (2008) Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer. Exp Gerontol 43(1):39–43. https://doi.org/10.1016/j.exger.2007.09.005
MacArthur J, Bowler E et al (2017) The new NHGRI-EBI catalog of published genome-wide association studies (GWAS catalog). Nucleic Acids Res 45(Database issue):D896–D901
Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L, Parkinson H (2014) The NHGRI GWAS catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42(Database issue):D1001–D1006. https://doi.org/10.1093/nar/gkt1229
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. https://doi.org/10.1086/519795
Zondervan KT, Cardon LR (2007) Designing candidate gene and genome-wide case-control association studies. Nat Protoc 2(10):2492–2501. https://doi.org/10.1038/nprot.2007.366
Hoggart CJ, Clark TG, De Iorio M, Whittaker JC, Balding DJ (2008) Genome-wide significance for dense SNP and resequencing data. Genet Epidemiol 32(2):179–185. https://doi.org/10.1002/gepi.20292
Seng KC, Seng CK (2008) The success of the genome-wide association approach: a brief story of a long struggle. Eur J Hum Genet 16(5):554–564. Bush WS, Moore JH (2012) Chapter 11: Genome-wide association studies. PLoS Comput Biol 8 (12):e1002822. doi:10.1371/journal.pcbi.1002822
Chanock S, NCI-NHGRI Working Group on Replication in Association Studies et al (2007) Replicating genotype-phenotype associations. Nature 447(7145):655–660. https://doi.org/10.1038/447655a
Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265. https://doi.org/10.1093/bioinformatics/bth457
Spain SL, Barrett JC (2015) Strategies for fine-mapping complex traits. Hum Mol Genet 24(R1):R111–R119. https://doi.org/10.1093/hmg/ddv260
Distefano JK, Taverna DM (2011) Review technological issues and experimental design of gene association studies. Methods Mol Biol 700:3–16
Clarke GM, Anderson CA, Pettersson FH, Cardon LR, Morris AP, Zondervan KT (2011) Basic statistical analysis in genetic case-control studies. Nat Protoc 6(2):121–133. https://doi.org/10.1038/nprot.2010.182
Skol AD, Scott LJ et al (2006) Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 5:554–564. https://doi.org/10.1038/ejhg.2008.12
Turner S, Armstrong LL, Bradford Y, Carlson CS, Crawford DC, Crenshaw AT, de Andrade M, Doheny KF, Haines JL, Hayes G, Jarvik G, Jiang L, Kullo IJ, Li R, Ling H, Manolio TA, Matsumoto M, McCarty CA, McDavid AN, Mirel DB, Paschall JE, Pugh EW, Rasmussen LV, Wilke RA, Zuvich RL, Ritchie MD (2011) Quality control procedures for genome-wide association studies. Curr Protoc Hum Genet Chapter 1:Unit1 19. doi:https://doi.org/10.1002/0471142905.hg0119s68
Auer PL, Lettre G (2015) Rare variant association studies: considerations, challenges and opportunities. Genome Med 7(1):16. https://doi.org/10.1186/s13073-015-0138-2
Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765–769
Zeggini E, Ioannidis JP (2009) Meta-analysis in genome-wide association studies. Pharmacogenomics 10(2):191–201. https://doi.org/10.2217/14622416.10.2.191
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Chang, M., He, L., Cai, L. (2018). An Overview of Genome-Wide Association Studies. In: Huang, T. (eds) Computational Systems Biology. Methods in Molecular Biology, vol 1754. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7717-8_6
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