Genome-Wide Association Studies of Intracranial Aneurysms: An Update

Intracranial aneurysms (IAs) affect 2% to 5% of the population and can have catastrophic results on rupture, accounting for 80% all of subarachnoid hemorrhages (SAHs).1–4 This medical and surgical emergency carries a 40% to 50% mortality rate, with 12% of individuals expiring before receiving any medical attention.5 Survivorship is fraught with socioeconomic challenges because two thirds of patients are left with some form of permanent neurological deficit.4 Although most IAs do not cause clinical symptoms during life,6,7 the substantial mortality rate with initial presentation underscores the importance of early diagnosis and intervention in high-risk groups. Advances in neuroimaging, microsurgical clipping, and minimally invasive endovascular modalities have helped reduce the burden of these morbid events; however, patient selection remains controversial given the unpredictable nature of aneurysm progression. Likewise, appropriate management is confounded by complex influences from environmental and genetic factors. Individuals aged 40 to 60 years are at highest risk for IAs, with women affected more than men by a 3:2 ratio.7,8 Other modifiable risk factors are hypertension, atherosclerosis, smoking, and alcohol consumption.9,10 In addition to aneurysm size and location within the cerebrovasculature, these factors are used clinically to assess rupture risk.7 Certain inherited syndromes predispose individuals to the formation of IAs, including Autosomal Dominant Polycystic Kidney Disease and Ehlers–Danlos syndrome.11–13 Although individuals with these syndromes should be screened with computed tomography or magnetic resonance angiography when there is family history of stroke or SAH, they account for only 10% of all cases.14 In the absence of known predisposing genetic mutations, individuals with first-degree relatives with IAs are 4× more likely to develop IAs themselves.15 Moreover, evidence shows that these aneurysms present earlier in life and rupture at smaller sizes compared …