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Article Dans Une Revue Genetic Epidemiology Année : 2019

A large‐scale exome array analysis of venous thromboembolism

1 University of Washington [Seattle]
2 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
3 Harvard T.H. Chan School of Public Health
4 BPH - Bordeaux population health
5 Rady Children's Hospital
6 UC San Diego - University of California [San Diego]
7 UiT - The Arctic University of Norway [Tromsø, Norway]
8 Framingham Heart Study
9 BU - Boston University [Boston]
10 Brigham and Women’s Hospital [Boston, MA]
11 University of Minnesota [MN, USA]
12 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
13 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
14 TIMONE - Hôpital de la Timone [CHU - APHM]
15 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
16 CRB TAC - Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM]
17 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
18 CNRGH - Centre National de Recherche en Génomique Humaine
19 JACOB - Institut de Biologie François JACOB
20 OSU - Ohio State University [Columbus]
21 UNN - University Hospital of North Norway [Tromsø]
22 Boston Veterans Administration Healthcare System
23 HEGP - Hôpital Européen Georges Pompidou [APHP]
24 KPWHRI - Kaiser Permanente Washington Health Research Institute [Seattle]
25 LA BioMed - Los Angeles Biomedical Research Institute
26 Seattle Epidemiologic Research and Information Center [Seattle]
27 Massachusetts General Hospital [Boston]
28 HMS - Harvard Medical School [Boston]
Rebecca Jackson
Peter Kraft

Résumé

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.
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Dates et versions

hal-02544372 , version 1 (18-06-2024)

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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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