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Journal Articles Genetic Epidemiology Year : 2019

A large‐scale exome array analysis of venous thromboembolism

Sara Lindström
  • Function : Author
Jennifer A Brody
  • Function : Author
Constance Turman
  • Function : Author
Marine Germain
  • Function : Author
Traci M. Bratz
  • Function : Author
Erin N Smith
  • Function : Author
Ming-Huei Chen
  • Function : Author
Marja Puurunen
  • Function : Author
Daniel Chasman
  • Function : Author
Jeffrey Hassler
  • Function : Author
Nathan Pankratz
  • Function : Author
Saonli Basu
  • Function : Author
Weihua Guan
  • Function : Author
Beata Gyorgy
Manal Ibrahim
  • Function : Author
Robert E Olaso
  • Function : Author
Rebecca Jackson
Sigrid Braekkan
  • Function : Author
Barbara Mcknight
  • Function : Author
Jean-Francois Deleuze
  • Function : Author
Christopher O'Donnel
  • Function : Author
Kelly Frazer
  • Function : Author
Bruce M Psary
  • Function : Author
Kerri L Wiggins
  • Function : Author
Kent D Taylor
  • Function : Author
Alexander P. Reiner
  • Function : Author
Susan R Heckbert
  • Function : Author
Charles Kooperberg
  • Function : Author
Paul Ridker
  • Function : Author
John-Bjarne Hansen
  • Function : Author
Weihong Tang
  • Function : Author
Andrew D Johnson
  • Function : Author
David-Alexandre Tregouet
  • Function : Author
Peter Kraft
Nicholas L. Smith
  • Function : Author
Christopher Kabrhel
  • Function : Author

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] similar to 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.

Dates and versions

hal-02544372 , version 1 (16-04-2020)

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Sara Lindström, Jennifer A Brody, Constance Turman, Marine Germain, Traci M. Bratz, et al.. A large‐scale exome array analysis of venous thromboembolism. Genetic Epidemiology, 2019, 43 (4), pp.449-457. ⟨10.1002/gepi.22187⟩. ⟨hal-02544372⟩
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