新科学想法 › 学术文库 › 学术文献 › 浏览文献

Clinical and Genetic Determinants of Varicose Veins

我爱微笑添加于 2018-12-31 21:50 | 896 次阅读 | 0 个评论

作者
Fukaya E, Flores AM, Lindholm D, Gustafsson S, Zanetti D, Ingelsson E, Leeper NJ
摘要
BACKGROUND: Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS: We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS: Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07x10(-16)). CONCLUSIONS: Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.
详细资料
- 关键词: epidemiology; genetics; genome-wide association study; varicose veins
- 文献种类: Journal Article
- 期刊名称: Circulation
- 期刊缩写: Circulation
- 期卷页: 2018年第138卷第25期 2869-2880页
- 地址: Stanford Cardiovascular Institute, CA (E.I., N.J.L.)
- ISBN: 0009-7322
学科领域生物医药 » 临床医学
相关链接 DOI URL