Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study

Sara Lindström, Marine Germain, Marta Crous-Bou, Erin N. Smith, Pierre Emmanuel Morange, Astrid van Hylckama Vlieg, Hugoline G. de Haan, Daniel Chasman, Paul Ridker, Jennifer Brody, Mariza De Andrade, John A. Heit, Weihong Tang, Immaculata DeVivo, Francine Grodstein, Nicholas L. Smith, David Tregouet, Christopher Kabrhel, the INVENT Consortium for the INVENT Consortium

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Abstract

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 × 10−6). 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.

Original languageEnglish (US)
Pages (from-to)897-902
Number of pages6
JournalHuman Genetics
Volume136
Issue number7
DOIs
StatePublished - Jul 1 2017

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Lindström, S., Germain, M., Crous-Bou, M., Smith, E. N., Morange, P. E., van Hylckama Vlieg, A., de Haan, H. G., Chasman, D., Ridker, P., Brody, J., De Andrade, M., Heit, J. A., Tang, W., DeVivo, I., Grodstein, F., Smith, N. L., Tregouet, D., Kabrhel, C., & for the INVENT Consortium, T. INVENT. C. (2017). Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Human Genetics, 136(7), 897-902. https://doi.org/10.1007/s00439-017-1811-x