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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 × 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 × 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 × 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;90:777-788.

BACKGROUND: General practitioners play an important role in diagnosis and ongoing management of pregnancies. Some GP registrars entering GP training may have had no post-graduate experience in obstetrics and gynaecology. GP registrars' involvement in antenatal care is under-researched. AIMS: This study aimed to determine the prevalence and associations of Australian GP registrars' clinical consultations involving antenatal care. MATERIALS AND METHODS: A cross-sectional analysis from the Registrar Clinical Encounters in Training (ReCEnT) cohort study. GP registrars record details of 60 consecutive consultations during each of three six-month training terms. Associations of managing pregnancy-related problems (compared to all other problems) were analysed using univariate and multivariable logistic regression. Independent variables included registrar, practice, patient, consultation and educational factors. RESULTS: Antenatal care comprised 3277 (1.1%) of registrar problems/diagnoses. Consultations involving pregnancy-related problems were significantly associated with registrars being female, in term three, younger, and having post-graduate qualifications in obstetrics/gynaecology. Patients were significantly more likely to be from a non-English speaking background. Pregnancy-related problems/diagnoses were more likely to be seen in lower socioeconomic areas. Consultation factors significantly associated with a pregnancy-related problem/diagnosis included ordering imaging, ordering pathology, arranging referrals, and a longer duration of consultation. Registrars were less likely to prescribe medication or generate learning goals. CONCLUSIONS: GP registrars see fewer antenatal problems compared to established GPs. Male registrars, especially, have significantly less exposure to antenatal care, suggesting potential limitation of opportunity to gain skills and experience in antenatal care.