RT Journal Article
SR Electronic
T1 Understanding genetic interactions and assessing the utility of the additive and multiplicative models through simulations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 706234
DO 10.1101/706234
A1 Lina-Marcela Diaz-Gallo
A1 Boel Brynedal
A1 Helga Westerlind
A1 Rickard Sandberg
A1 Daniel Ramsköld
YR 2019
UL http://biorxiv.org/content/early/2019/07/18/706234.abstract
AB Interaction analysis is used to investigate the effect which two risk factors have on each other, and on disease risk. To study interactions, both additive and multiplicative models have been used, although their interpretations are not universally understood. In this study, we simulated several scenarios of risk factors relationships and investigated the resulting interactions using additive or multiplicative models. Independent risk factors approach additive effect at low disease prevalence, showing a sub-additive relationship. However, risk factors that contribute to the same chain of events (i.e. have synergy) lead to multiplicative relative risk. Thresholds on the number of required risk factors lead to intermediaries between additive and multiplicative risk. We proposed a novel metric of interaction consistent with additive, multiplicative and multifactorial threshold models. Finally, we demonstrate the utility of the simulation-strategy and discovered relationships by analyzing and interpreting gene-gene odds ratios obtained in a rheumatoid arthritis cohort.