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

Sara Lindström (1) , Marine Germain (2) , Marta Crous-Bou , Erin N. Smith (3) , Pierre-Emmanuel Morange (4, 5) , Astrid van Hylckama Vlieg (6) , Hugoline de Haan (7) , Daniel Chasman (8) , Paul Ridker (8) , Jennifer Brody , Mariza de Andrade (9) , John Heit (10) , Weihong Tang (11) , Immaculata Devivo , Francine Grodstein (12) , Nicholas L Smith , David A. Tregouet (13) , Christopher Kabrhel (14)

1 PGESG - BOSTON - Program in Genetic Epidemiology and Statistical Genetics
2 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
3 The Scripps Translational Science Institute and Scripps Health
4 Fibrinolyse et Pathologie Vasculaire
5 NORT - Nutrition, obésité et risque thrombotique
6 LEIDEN - DTH - Department of Thrombosis and Hemostasis
7 Department of Thrombosis and Haemostasis
8 Brigham and Women's Hospital [Boston]
9 HSR - Department of Health Sciences Research [Mayo Clinic]
10 Division of Cardiovascular Diseases
11 UMN - University of Minnesota [Twin Cities]
12 Department of Epidemiology
13 Génétique épidémiologique et moléculaire des pathologies cardiovasculaires
14 Massachusetts General Hospital [Boston]

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.

Keywords: SNP; venous thromboembolism; Mendelian randomization; association; Obesity

Domains: Life Sciences [q-bio]; Santé publique et épidémiologie; Life Sciences [q-bio]; Human health and pathology; Cardiology and cardiovascular system; Life Sciences [q-bio]; Human health and pathology; Endocrinology and metabolism

Sara Lindström, Marine Germain, Marta Crous-Bou, Erin N. Smith, Pierre-Emmanuel Morange, et al.. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Human Genetics, 2017, 136 (7), pp.897-902. ⟨10.1007/s00439-017-1811-x⟩. ⟨hal-01753834⟩