TY - JOUR
T1 - Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study
AU - Lindström, Sara
AU - Germain, Marine
AU - Crous-Bou, Marta
AU - Smith, Erin N.
AU - Morange, Pierre Emmanuel
AU - van Hylckama Vlieg, Astrid
AU - de Haan, Hugoline G.
AU - Chasman, Daniel
AU - Ridker, Paul
AU - Brody, Jennifer
AU - de Andrade, Mariza
AU - Heit, John A.
AU - Tang, Weihong
AU - DeVivo, Immaculata
AU - Grodstein, Francine
AU - Smith, Nicholas L.
AU - Tregouet, David
AU - Kabrhel, Christopher
AU - For The Invent Consortium
N1 - Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
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 × 10−6). 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.
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U2 - 10.1007/s00439-017-1811-x
DO - 10.1007/s00439-017-1811-x
M3 - Article
C2 - 28528403
AN - SCOPUS:85019574058
SN - 0340-6717
VL - 136
SP - 897
EP - 902
JO - Human Genetics
JF - Human Genetics
IS - 7
ER -