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

doi:10.1007/s00439-017-1811-x

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

Research output: Contribution to journal › Article › peer-review

18 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 language	English (US)
Pages (from-to)	897-902
Number of pages	6
Journal	Human genetics
Volume	136
Issue number	7
DOIs	https://doi.org/10.1007/s00439-017-1811-x
State	Published - Jul 1 2017

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1007/s00439-017-1811-x

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

Lindström, S, Germain, M, Crous-Bou, M, Smith, EN, Morange, PE, van Hylckama Vlieg, A, de Haan, HG, Chasman, D, Ridker, P, Brody, J, de Andrade, M, Heit, JA, Tang, W, DeVivo, I, Grodstein, F, Smith, NL, Tregouet, D, Kabrhel, C & for the INVENT Consortium, TINVENTC 2017, 'Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study', Human genetics, vol. 136, no. 7, pp. 897-902. https://doi.org/10.1007/s00439-017-1811-x

@article{705b98679d5643d58a3c5e38582f4920,

title = "Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2017, Springer-Verlag Berlin Heidelberg.",

year = "2017",

month = jul,

day = "1",

doi = "10.1007/s00439-017-1811-x",

language = "English (US)",

volume = "136",

pages = "897--902",

journal = "Human genetics",

issn = "0340-6717",

publisher = "Springer Verlag",

number = "7",

}

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, the INVENT Consortium

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.

UR - http://www.scopus.com/inward/record.url?scp=85019574058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019574058&partnerID=8YFLogxK

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 -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this