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, For The Invent Consortium

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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

Bibliographical note

Funding Information:
This work was supported by National Health Lung and Blood Institute Grants HL116854, HL43201, HL60739, HL68986, HL73410, HL74745, HL85251, HL107442, HL66261, HL83141, HL59367 and HL95080 and the National Human Genome Research Institute (HG04735). The Nurses’ Health Study, Nurses’ Health Study II and Health Professionals Follow up Study are supported by the National Cancer Institute (CA186107, CA176726, CA167552). The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and CA182913). This work was partially supported by the GenMed LABEX (ANR-10-LABX-0013) and the ICAN Institute for Cardiometabolism and Nutrition (ANR-10-IAHU-05) and an independent grant from the K.G. Jebsen Foundation in Norway.

Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.

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