@article {6906, title = {Lifetime Risk of Venous Thromboembolism in Two Cohort Studies.}, journal = {Am J Med}, volume = {129}, year = {2016}, month = {2016 Mar}, pages = {339.e19-26}, abstract = {

BACKGROUND: Greater public awareness of venous thromboembolism may be an important next step for optimizing venous thromboembolism prevention and treatment. "Lifetime risk" is an easily interpretable way of presenting risk information. Therefore, we sought to calculate the lifetime risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism) using data from 2 large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study.

METHODS: We followed participants aged 45-64 years in ARIC (n = 14,185) and >=65 in CHS (n = 5414) at baseline visits (1987-1989 in ARIC, 1989-1990 and 1992-1993 in CHS) for incident venous thromboembolism (n = 728 in ARIC through 2011 and n = 172 in CHS through 2001). We estimated lifetime risks and 95\% confidence intervals of incident venous thromboembolism using a modified Kaplan-Meier method, accounting for the competing risk of death from other causes.

RESULTS: At age 45 years, the remaining lifetime risk of venous thromboembolism in ARIC was 8.1\% (95\% confidence interval, 7.1-8.7). High-risk groups were African Americans (11.5\% lifetime risk), those with obesity (10.9\%), heterozygous for the factor V Leiden (17.1\%), or with sickle cell trait or disease (18.2\%). Lifetime risk estimates differed by cohort; these differences were explained by differences in time period of venous thromboembolism ascertainment.

CONCLUSIONS: At least 1 in 12 middle-aged adults will develop venous thromboembolism in their remaining lifetime. This estimate of lifetime risk may be useful to promote awareness of venous thromboembolism and guide decisions at both clinical and policy levels.

}, keywords = {African Continental Ancestry Group, Aged, Anemia, Sickle Cell, Cohort Studies, Factor V, Follow-Up Studies, Heterozygote, Humans, Kaplan-Meier Estimate, Middle Aged, Obesity, Risk, Sickle Cell Trait, United States, Venous Thromboembolism}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2015.10.014}, author = {Bell, Elizabeth J and Lutsey, Pamela L and Basu, Saonli and Cushman, Mary and Heckbert, Susan R and Lloyd-Jones, Donald M and Folsom, Aaron R} } @article {7979, title = {A large-scale exome array analysis of venous thromboembolism.}, journal = {Genet Epidemiol}, year = {2019}, month = {2019 Jan 19}, abstract = {

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08\%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80\% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.

}, issn = {1098-2272}, doi = {10.1002/gepi.22187}, author = {Lindstr{\"o}m, Sara and Brody, Jennifer A and Turman, Constance and Germain, Marine and Bartz, Traci M and Smith, Erin N and Chen, Ming-Huei and Puurunen, Marja and Chasman, Daniel and Hassler, Jeffrey and Pankratz, Nathan and Basu, Saonli and Guan, Weihua and Gyorgy, Beata and Ibrahim, Manal and Empana, Jean-Philippe and Olaso, Robert and Jackson, Rebecca and Braekkan, Sigrid K and McKnight, Barbara and Deleuze, Jean-Francois and O{\textquoteright}Donnell, Cristopher J and Jouven, Xavier and Frazer, Kelly A and Psaty, Bruce M and Wiggins, Kerri L and Taylor, Kent and Reiner, Alexander P and Heckbert, Susan R and Kooperberg, Charles and Ridker, Paul and Hansen, John-Bjarne and Tang, Weihong and Johnson, Andrew D and Morange, Pierre-Emmanuel and Tr{\'e}gou{\"e}t, David A and Kraft, Peter and Smith, Nicholas L and Kabrhel, Christopher} }