TY - JOUR T1 - Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. JF - Hum Genet Y1 - 2017 A1 - Lindström, Sara A1 - Germain, Marine A1 - Crous-Bou, Marta A1 - Smith, Erin N A1 - Morange, Pierre-Emmanuel A1 - van Hylckama Vlieg, Astrid A1 - de Haan, Hugoline G A1 - Chasman, Daniel A1 - Ridker, Paul A1 - Brody, Jennifer A1 - de Andrade, Mariza A1 - Heit, John A A1 - Tang, Weihong A1 - DeVivo, Immaculata A1 - Grodstein, Francine A1 - Smith, Nicholas L A1 - Tregouet, David A1 - Kabrhel, Christopher KW - Adult KW - Body Mass Index KW - Case-Control Studies KW - European Continental Ancestry Group KW - Female KW - Genome-Wide Association Study KW - Humans KW - Incidence KW - Logistic Models KW - Male KW - Mendelian Randomization Analysis KW - Obesity KW - Polymorphism, Single Nucleotide KW - Proportional Hazards Models KW - Venous Thromboembolism AB -

Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P < 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02-1.12, P = 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30-1.93 per standard deviation increase in BMI, P = 5.8 × 10). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE.

VL - 136 IS - 7 ER -