Multi-ancestry genome-wide analysis identifies shared genetic effects and common genetic variants for self-reported sleep duration.

Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.

Effect of genetic liability to migraine on coronary artery disease and atrial fibrillation: a Mendelian randomization study.

BACKGROUND AND PURPOSE: Observational studies have implicated migraine as a risk factor for coronary artery disease (CAD) and atrial fibrillation (AF); however, it is unclear whether migraine is causal in this relationship. Potential causality between genetically instrumented liability to migraine and cardiovascular disease outcomes was investigated using two-sample Mendelian randomization. METHODS: The exposure comprised 35 independent, genome-wide significant genetic variants identified in the largest published genome-wide association study of migraine (Ncases  = 59 674/Ncontrols = 316 078). The outcome datasets included genome-wide association studies of CAD (76 014/264 785), myocardial infarction (43 676/128 199), angina (10 618/326 065) and AF (60 620/970 216). Mendelian randomization estimates were calculated using inverse-variance weighted regression, and were further assessed with conventional Mendelian randomization sensitivity analyses. RESULTS: Evidence was found for a protective effect of migraine liability on CAD (odds ratio 0.86, 95% confidence interval 0.76-0.96, P = 0.003), myocardial infarction (0.86, 0.74-0.96, P = 0.01) and angina (0.86, 0.75-0.99, P = 0.04), but not on AF (1.00, 0.95-1.05, P = 0.88). Analyses by migraine subtype showed an effect of liability to migraine without aura on CAD risk (0.91, 0.84-0.99, P = 0.014), but not of migraine with aura (1.00, 0.97-1.03, P = 0.89). Sensitivity analyses indicated minimal bias by horizontal pleiotropy, outliers, reverse causality or sample overlap. CONCLUSIONS: A potentially protective effect of genetically instrumented liability to migraine on CAD risk was identified. Mechanistic research investigating this link is warranted.