Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Nov 12;8(21):5710-5718.
doi: 10.1182/bloodadvances.2024014252.

Ancestry-independent risk of venous thromboembolism in individuals with sickle cell trait vs factor V Leiden

Keng-Han Lin  1 , Julie M Granka  1 , Anjali J Shastri  1 , Vence L Bonham  2 , Rakhi P Naik  3
Affiliations
Meta-Analysis

Ancestry-independent risk of venous thromboembolism in individuals with sickle cell trait vs factor V Leiden

Keng-Han Lin et al. Blood Adv. .

Abstract

Sickle cell trait (SCT) is a risk factor for venous thromboembolism (VTE). Prior studies investigating the association between SCT and VTE have been performed nearly exclusively in Black populations. However, race-based research can contribute to systemic racism in medicine. We leveraged data from the 23andMe research cohort (4 184 082 participants) to calculate the ancestry-independent risk of VTE associated with SCT as well as comparative risk estimates for heterozygous factor V Leiden (FVL). Odds ratios (ORs) were calculated using a meta-analysis of 3 genetic ancestry groups (European [n = 3 183 142], Latine [n = 597 539], and African [n = 202 281]) and a secondary full-cohort analysis including 2 additional groups (East Asian [n = 159 863] and South Asian [n = 41 257]). Among the full cohort, 94 323 participants (2.25%) reported a history of VTE. On meta-analysis, individuals with SCT had a 1.45-fold (confidence interval [CI], 1.32-1.60) increased risk of VTE compared with SCT noncarriers, which was similar to the full-cohort estimate. The risk of pulmonary embolism (PE) in SCT (OR, 1.95; CI, 1.72-2.20) was higher than that of isolated deep venous thrombosis (DVT; OR, 1.04; CI, 0.90-1.21). FVL carriers had 3.30-fold (CI, 3.24-3.37) increased risk of VTE compared with FVL noncarriers, with a higher risk of isolated DVT (OR, 3.59; CI, 3.51-3.68) than PE (OR, 2.72; CI, 2.64-2.81). In this large, diverse cohort, the risk of VTE was increased among individuals with SCT compared with those without, independent of race or genetic ancestry. The risk of VTE with SCT was lower than that observed in FVL; however, the pattern of VTE in SCT was PE predominant, which is the opposite to that observed in FVL.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: K.-H.L., J.M.G., and A.J.S. are employed by and hold stock or stock options in 23andMe Inc. The remaining authors declare no competing financial interests.

A complete list of the members of the 23andMe Research Team appears in “Appendix.”

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Risk estimates for VTE in sickle cell trait. (A-C) Meta-analysis of ORs for VTE, PE, and isolated DVT, respectively, comparing SCT carriers with noncarriers. (D) Meta-analysis estimate for PE vs isolated DVT comparing SCT carriers with noncarriers.
Figure 2.
Figure 2.
Risk estimates for VTE in factor V leiden. (A) Meta-analysis of ORs for VTE (i), PE (ii), and isolated DVT (iii) comparing FVL carriers with noncarriers. (B) Meta-analysis estimate for PE vs isolated DVT comparing FVL carriers with noncarriers.
See this image and copyright information in PMC

References

    1. Grant AM, Parker CS, Jordan LB, et al. Public health implications of sickle cell trait: a report of the CDC meeting. Am J Prev Med. 2011;41(6 suppl 4):435–S439. - PubMed
    1. Lindenau JD, Wagner SC, Castro SMd, Hutz MH. The effects of old and recent migration waves in the distribution of HBB∗S globin gene haplotypes. Genet Mol Biol. 2016;39(4):515–523. - PMC - PubMed
    1. Power-Hays A, McGann PT. When actions speak louder than words - racism and sickle cell disease. N Engl J Med. 2020;383(20):1902–1903. - PubMed
    1. Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018;169(9):619–627. - PMC - PubMed
    1. Austin H, Key NS, Benson JM, et al. Sickle cell trait and the risk of venous thromboembolism among blacks. Blood. 2007;110(3):908–912. - PubMed

Publication types