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Rationale Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

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WHAT THIS PAPER ADDS This is the largest systematic review and meta-analysis detailing the presentation, management, and procedural complications following carotid body tumour (CBT) surgery. Although relatively rare, complications associated with CBT are not inconsiderable, especially in the more challenging Shamblin III CBTs where procedural stroke rates were about 4%, while cranial nerve injury rates approached 20%. The increasing morbidity associated with Shamblin III tumours must be considered during the consent process.Objectives: The aim was to determine the mode of presentation and 30 day procedural risks in 4418 patients with 4743 carotid body tumours (CBTs) undergoing surgical excision. Methods: This is a systematic review and meta-analysis of 104 observational studies. Results: Overall, 4418 patients with 4743 CBTs were identified. The mean age was 47 years, with the majority being female (65%). The commonest presentation was a neck mass (75%), of which 85% were painless. Dysphagia, cranial nerve injury (CNI), and headache were present in 3%, while virtually no one presented with a transient ischaemic attack (0.26%) or stroke (0.09%). The majority (97%) underwent excision, but only 21% underwent pre-operative embolisation. Overall, 27% were Shamblin I CBTs; 44% were Shamblin II; and 29% were Shamblin III. The mean 30 day mortality was 2.29% (95% CI 1.79e2.93). The mean 30 day stroke rate was 3.53% (95% CI 2.91e4.29), while the mean 30 day CNI rate was 25.4% (95% CI 24.5e31.22). The prevalence of persisting CNI at 30 days was 11.15% (95% CI 8.42e14.64). Twelve series (544 patients) correlated 30 day stroke with Shamblin status. Shamblin I CBTs were associated with a 1.89% stroke rate (95% CI 0.92e3.82), increasing to 2.71% (95% CI 1.43e5.07) for Shamblin II CBTs and 3.99% (95% CI 2.34e 6.74) for Shamblin III tumours. Twenty-six series (1075 patients) correlated CNI rates with Shamblin status: 3.76% (95% CI 2.62e5.35) for Shamblin I CBTs, 14.14% (95% CI 11.94e16.68) for Shamblin II, and 17.10% (95% CI 14.82e19.65) for Shamblin III tumours. The prevalence of neck haematoma requiring re-exploration was 5.24% (95% CI 3.45e7.91). The proportion of patients with a neck haematoma requiring re-exploration was not reduced by pre-operative embolisation (5.92%; 95% CI 2.56e13.08) vs. no embolisation (5.82%; 95% CI 2.76e11.88). Pre-operative embolisation did not reduce drainage losses (639 mL vs. 653 mL). Conclusions: This is the largest meta-analysis of outcomes after CBT excision. Procedural risks associated with tumour excision were considerable, especially with Shamblin III tumours where 4% suffered a peri-operative stroke and 17% suffered a CNI.