Lindström Sara, Germain Marine, Crous-Bou Marta, Smith Erin N, Morange Pierre-Emmanuel, van Hylckama Vlieg Astrid, de Haan Hugoline G, Chasman Daniel, Ridker Paul, Brody Jennifer, de Andrade Mariza, Heit John A, Tang Weihong, DeVivo Immaculata, Grodstein Francine, Smith Nicholas L, Tregouet David, Kabrhel Christopher
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics and Pathophysiology of Cardiovascular Diseases, Paris, France.
Hum Genet. 2017 Jul;136(7):897-902. doi: 10.1007/s00439-017-1811-x. Epub 2017 May 20.
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). 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.
观察性研究表明肥胖与静脉血栓栓塞（VTE）之间存在关联，但由于反向因果关系或混杂偏倚，尚不清楚所观察到的关联是否具有因果性。我们进行了一项关于体重指数（BMI）与VTE的孟德尔随机化研究。我们鉴定出95个先前与BMI相关的单核苷酸多态性（SNP），并利用来自INVENT联盟先前进行的全基因组关联研究（GWAS）的数据，评估了基因预测的高BMI与VTE之间的关联，该联盟共有7507例VTE病例和52632例欧洲血统对照。5个BMI SNP与VTE的关联在P < 0.05水平上具有统计学意义，其中FTO SNP rs1558902的关联最强（OR 1.07，95% CI 1.02 - 1.12，P = 0.005）。此外，我们观察到基因预测的BMI与VTE之间存在显著关联（BMI每增加一个标准差，OR =
1.59，95% CI 1.30 - 1.93，P = 5.8 × 10）。我们的研究为高BMI与VTE风险之间的因果关系提供了证据。降低肥胖水平可能会导致VTE发病率降低。
