title: Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis.
abstract: Gene-environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92-10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79-2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59-2.59; excess risk due to interaction=3.30, 95%CI=0.47-6.12; attributable proportion due to interaction=45%, 95% CI=22-68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene-environment interactions on both a multiplicative and additive scale.
authors: Department of Physiology, Anatomy and Genetics and Medical Research Council Functional Genomics Unit, University of Oxford, UK.
authors: Giulio
authors: G
authors: Disanto
authors: Carolina
authors: C
authors: Hall
authors: Robyn
authors: R
authors: Lucas
authors: Anne-Louise
authors: AL
authors: Ponsonby
authors: Antonio J
authors: AJ
authors: Berlanga-Taylor
authors: Gavin
authors: G
authors: Giovannoni
authors: Sreeram V
authors: SV
authors: Ramagopalan
mesh_terms: D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007244:Infectious Mononucleosis / Q000150:complications*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000821:virology*; D015999:Multivariate Analysis; D012307:Risk Factors
chemical_list: D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen
keywords: HLA-DRB1*15; infectious mononucleosis; interaction; multiple sclerosis