Atrial fibrillation (AF) affects over 33 million individuals worldwide1 and has a complex heritability.2 We conducted the largest meta-analysis of genome-wide association studies for AF to date, consisting of over half a million individuals including 65,446 with AF. In total, we identified 97 loci significantly associated with AF including 67 of which were novel in a combined-ancestry analysis, and 3 in a European specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait loci (eQTL) analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Spontaneous intracranial artery dissection is an uncommon and probably underdiagnosed cause of stroke that is defi ned by the occurrence of a haematoma in the wall of an intracranial artery. Patients can present with headache, ischaemic stroke, subarachnoid haemorrhage, or symptoms associated with mass eff ect, mostly on the brainstem. Although intracranial artery dissection is less common than cervical artery dissection in adults of European ethnic origin, intracranial artery dissection is reportedly more common in children and in Asian populations. Risk factors and mechanisms are poorly understood, and diagnosis is challenging because characteristic imaging features can be diffi cult to detect in view of the small size of intracranial arteries. Therefore, multimodal follow-up imaging is often needed to confi rm the diagnosis. Treatment of intracranial artery dissections is empirical in the absence of data from randomised controlled trials. Most patients with subarachnoid haemorrhage undergo surgical or endovascular treatment to prevent rebleeding, whereas patients with intracranial artery dissection and cerebral ischaemia are treated with antithrombotics. Prognosis seems worse in patients with subarachnoid haemorrhage than in those without.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Background and Purpose-Migraine with aura is associated with ischemic stroke, but few studies have investigated the clinical and anatomic features of this association. We assessed the association of probable migraine with and without visual aura with ischemic stroke within subgroups defined by stroke subtype, vascular territory, probable migraine characteristics, and other clinical features. Methods-Using data from a population-based, case-control study, we studied 386 women ages 15 to 49 years with first ischemic stroke and 614 age-and ethnicity-matched controls. Based on their responses to a questionnaire on headache symptoms, subjects were classified as having no migraine, probable migraine without visual aura, or probable migraine with visual aura (PMVA). Results-Women with PMVA had 1.5 greater odds of ischemic stroke (95% CI, 1.1 to 2.0); the risk was highest in those with no history of hypertension, diabetes, or myocardial infarction compared to women with no migraine. Women with PMVA who were current cigarette smokers and current users of oral contraceptives had 7.0-fold higher odds of stroke (95% CI, 1.3 to 22.8) than did women with PMVA who were nonsmokers and non-oral contraceptive users. Women with onset of PMVA within the previous year had 6.9-fold higher adjusted odds of stroke (95% CI, 2.3 to 21.2) compared to women with no history of migraine. Conclusions-PMVA was associated with an increased risk of stroke, particularly among women without other medical conditions associated with stroke. Behavioral risk factors, specifically smoking and oral contraceptive use, markedly increased the risk of PMVA, as did recent onset of PMVA.