2 results on '"Astrid van Hylckama, Vlieg"'
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2. Genome-Wide Association Study Identifies a Novel Genetic Risk Factor for Recurrent Venous Thrombosis
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Hugoline G. de Haan, Astrid van Hylckama Vlieg, David-Alexandre Trégouët, Jean-François Deleuze, Frits R. Rosendaal, Marine Germain, Trevor Baglin, Universiteit Leiden, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Netherlands Heart Foundation [NHS98.113, NHS208B086, 89.063], Dutch Cancer Foundation [RUL 99/1992], Netherlands Organization for Scientific Research [912-03-033vertical bar2003, 916.56.157], follow-up study by grant Prevention Fund/ZonMW [2827170], ANR-10-IAHU-0005,ICAN,Institut de Cardiologie-Métabolisme-Nutrition(2010), ANR-10-LABX-0013,GENMED,Medical Genomics(2010), Universiteit Leiden [Leiden], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
0301 basic medicine ,Recurrent venous thrombosis ,genome-wide association study ,business.industry ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Bioinformatics ,Thrombophilia ,Recurrence risk ,03 medical and health sciences ,Venous thrombosis ,030104 developmental biology ,0302 clinical medicine ,factor V Leiden ,Factor V Leiden ,medicine ,risk factors ,venous thrombosis ,Genetic risk ,Genetic risk factor ,business ,thrombophilia - Abstract
Background: Genetic risk factors for a first venous thrombosis (VT) seem to have little effect on recurrence risk. Therefore, we aimed specifically to identify novel genetic determinants of recurrent VT. To date, genome-wide association studies are lacking. Methods and Results: We performed a genome-wide association scan in 1279 patients from the MEGA (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis) follow-up study; 832 patients who remained recurrence free during a median follow-up time of 6.1 years and 447 recurrent VT patients with a median time-to-recurrence of 2.6 years. We analyzed genotype probabilities of ≈8.6 million variants, imputed to the Genome of the Netherlands project reference panel, with a minor allele frequency ≥1% for an association with recurrent VT. One region exceeded genome-wide significance ( P ≤5×10 − 8 ), mapping to the well-known factor V Leiden locus. Conditional association analyses on factor V Leiden did not yield any secondary association signals. We also identified 52 suggestive association signals ( P −5 ) at 17 additional loci. None of these loci were previously implicated in VT risk. Replication analyses for 17 lead variants were performed in 350 patients with recurrent VT and 1866 patients with a single VT event from the MEGA follow-up study, THE-VTE (Thrombophilia, Hypercoagulability and Environmental Risks in Venous Thromboembolism) study, and LETS (Leiden Thrombophilia Study). We observed an association with recurrence for an intergenic variant at 18q22.1 with an odds ratio of 1.7 (95% confidence interval, 1.2–2.6) per copy of the minor allele. Conclusions: We confirmed the association of factor V Leiden and identified a novel risk locus at 18q22.1 in the first large genetic study on recurrent VT.
- Published
- 2018
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