@article{3031742,
    title = "Genome-Wide Association Study Identifies First Locus Associated with
Susceptibility to Cerebral Venous Thrombosis",
    author = "Ken-Dror, Gie and Cotlarciuc, Ioana and Martinelli, Ida and Grandone, and Elvira and Hiltunen, Sini and Lindgren, Erik and Margaglione, Maurizio and and Duchez, Veronique Le Cam and Triquenot, Aude Bagan and Zedde, and Marialuisa and Mancuso, Michelangelo and Ruigrok, Ynte M. and Marjot, and Thomas and Worrall, Brad and Majersik, Jennifer J. and Metso, Tiina M. and and Putaala, Jukka and Haapaniemi, Elena and Zuurbier, Susanna M. and and Brouwer, Matthijs C. and Passamonti, Serena M. and Abbattista, Maria and and Bucciarelli, Paolo and Mitchell, Braxton D. and Kittner, Steven J. and and Lemmens, Robin and Jern, Christina and Pappalardo, Emanuela and Costa, and Paolo and Colombi, Marina and de Sousa, Diana Aguiar and Rodrigues, and Sofia and Canhao, Patricia and Tkach, Aleksander and Santacroce, Rosa and and Favuzzi, Giovanni and Arauz, Antonio and Colaizzo, Donatella and and Spengos, Kostas and Hodge, Amanda and Ditta, Reina and Pezzini, and Alessandro and Debette, Stephanie and Coutinho, Jonathan M. and Thijs, and Vincent and Jood, Katarina and Pare, Guillaume and Tatlisumak, Turgut and and Ferro, Jose M. and Sharma, Pankaj",
    journal = "Annals of Neurology",
    year = "2021",
    volume = "90",
    number = "5",
    pages = "777-788",
    publisher = "Wiley",
    issn = "0364-5134, 1531-8249",
    doi = "10.1002/ana.26205",
    abstract = "Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke
affecting mostly young individuals. Although genetic factors are thought
to play a role in this cerebrovascular condition, its genetic etiology
is not well understood. Methods A genome-wide association study was
performed to identify genetic variants influencing susceptibility to
CVT. A 2-stage genome-wide study was undertaken in 882 Europeans
diagnosed with CVT and 1,205 ethnicity-matched control subjects divided
into discovery and independent replication datasets. Results In the
overall case-control cohort, we identified highly significant
associations with 37 single nucleotide polymorphisms (SNPs) within the
9q34.2 region. The strongest association was with rs8176645 (combined p
= 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval
[CI] = 1.76-2.31). The discovery set findings were validated across an
independent European cohort. Genetic risk score for this 9q34.2 region
increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20,
p = 2.00 x 10(-16)). SNPs within this region were in strong linkage
disequilibrium (LD) with coding regions of the ABO gene. The ABO blood
group was determined using allele combination of SNPs rs8176746 and
rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI =
2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with
individuals with blood group O. Interpretation We present the first
chromosomal region to robustly associate with a genetic susceptibility
to CVT. This region more than doubles the likelihood of CVT, a risk
greater than any previously identified thrombophilia genetic risk
marker. That the identified variant is in strong LD with the coding
region of the ABO gene with differences in blood group prevalence
provides important new insights into the pathophysiology of CVT. ANN
NEUROL 2021"
}