TY - JOUR
T1 - Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis
AU - Disanto, Giulio
AU - Hall, Carolina
AU - Lucas, Robyn
AU - Ponsonby, Anne Louise
AU - Berlanga-Taylor, Antonio J.
AU - Giovannoni, Gavin
AU - Ramagopalan, Sreeram V.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - HLA-DRB115
KW - infectious mononucleosis
KW - interaction
KW - multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=84883315613&partnerID=8YFLogxK
U2 - 10.1177/1352458513477231
DO - 10.1177/1352458513477231
M3 - Article
SN - 1352-4585
VL - 19
SP - 1355
EP - 1358
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 10
ER -