Disease Model Distortion in Association Studies
Damjan Vukcevic, Eliana Hechter, Chris Spencer, Peter Donnelly
Genetic Epidemiology | WILEY | Published : 2011
Most findings from genome-wide association studies (GWAS) are consistent with a simple disease model at a single nucleotide polymorphism, in which each additional copy of the risk allele increases risk by the same multiplicative factor, in contrast to dominance or interaction effects. As others have noted, departures from this multiplicative model are difficult to detect. Here, we seek to quantify this both analytically and empirically. We show that imperfect linkage disequilibrium (LD) between causal and marker loci distorts disease models, with the power to detect such departures dropping off very quickly: decaying as a function of r4, where r2 is the usual correlation between the causal a..View full abstract
Awarded by Wellcome Trust
Contract grant sponsor: Wellcome Trust; Contract grant numbers: 085475/Z/08/Z; 085475/Z/08/Z; 075491/Z/04; Contract grant sponsor: Rhodes Trust and Commonwealth Scholarship and Fellowship Plan.