Synthetic associations created by rare variants do not explain most GWAS results

• Published in: PLoS biology Vol. 9; no. 1; p. e1000579
• Main Authors: Wray, Naomi R, Purcell, Shaun M, Visscher, Peter M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-01-2011; Public Library of Science (PLoS)
• Subjects: Computer Simulation; Diabetes; Disease; Genes; Genetic Loci; Genetic Variation; Genetics; Genetics and Genomics/Complex Traits; Genetics and Genomics/Disease Models; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Population Genetics; Genome-Wide Association Study; Genomes; Haplotypes; Humans; Linkage Disequilibrium; Models, Genetic; Multifactorial Inheritance; Mutation; Population genetics; Schizophrenia; Schizophrenia - genetics; Single nucleotide polymorphisms; Studies; Synthetic biology; Australia; United States
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1000579

Abbreviations: GRR, genotype relative risk; GWAS, genome-wide association study; ISC, International Schizophrenia Consortium; LD, linkage disequilibrium; MAF, minor allele frequency; OR, odds ratio; RAF, risk allele frequency; SNP, single nucleotide polymorphism Introduction Complex traits and diseases, such as body-mass index, height, diabetes, heart disease, and psychiatric disorders are undoubtedly caused by multiple genetic and environmental factors, although it has been a major challenge to identify specific genes. Within a 100 kb region up to 9 causal SNPs, each with frequency between 0.005 and 0.02 were allocated to influence disease (causal SNPs). [...]at a locus with 9 such variants, ~20% of the general population would be expected to carry at least one disease risk allele.