Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study

Gie Ken Dror, Ida Martinelli, Elvira Grandone, Sini Hiltunen, Erik Lindgren, Maurizio Margaglione, Veronique Le Cam Duchez, Aude B. Triquenot, Marialuisa Zedde, Michelangelo Mancuso, Ynte M. Ruigrok, Bradford B Worrall, Jennifer J Majersik, Jukka Putaala, Elena Haapaniemi, Susanna Zuurbier, Matthijs C Brouwer, Serena M Passamonti, Maria Abbattista, Paolo BucciarelliRobin Lemmens, Emanuela Pappalardo, Paolo Costa, Marina Colombi, Diana Aguiar de Sousa, Sofia G. Rodrigues, Patrícia Canhão, Aleksander Tkach, Rosa Santacroce, Giovanni Favuzzi, Antonio Arauz, Donatella Colaizzo, Konstantinos Spengos, Amanda Hodge, Reina Ditta, Alessandro Pezzini, Jonathan M Coutinho, Vincent N Thijs, Katarina Jood, Guillaume Pare, Turgut Tatlisumak, José M Ferro, Pankaj Sharma

Research output: Contribution to journalArticlepeer-review


Background and Objectives

Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT.


Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status.


We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74–5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64–26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54–10.33, p = 2.00e15), compared with blood group-O combined with AA.


Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.
Original languageEnglish
Issue number11
Early online date17 May 2024
Publication statusPublished - 11 Jun 2024

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