Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.publishedVersionPeer reviewe

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH) Finnish innovation fund Sitra Finska Lakaresallskapet Academy of Finland Sigrid Juselius Foundation Academy of Finland Appeared in source as:Academy of Finland Center of Excellence in Complex Disease Genetics Finnish Foundation for Cardiovascular Research Novo Nordisk Foundation Novocure Limited CANDY foundation (CEHEAD) South-Eastern Norway Regional Health Authorit

Prospects for Galactic and stellar astrophysics with asteroseismology of giant stars in the TESS continuous viewing zones and beyond

The NASA-$\it{TESS}$ mission presents a treasure trove for understanding the stars it observes and the Milky Way, in which they reside. We present a first look at the prospects for Galactic and stellar astrophysics by performing initial asteroseismic analyses of bright ($G < 11$) red giant stars in the $\it{TESS}$ Southern Continuous Viewing Zone (SCVZ). Using three independent pipelines, we detect $\nu_{\mathrm{max}}$ and $\Delta\nu$ in 41% of the 15,405 star parent sample (6,388 stars), with consistency at a level of $\sim 2\%$ in $\nu_{\mathrm{max}}$ and $\sim 5\%$ in $\Delta\nu$. Based on this, we predict that seismology will be attainable for $\sim 3\times10^{5}$ giants across the whole sky, subject to improvements in analysis and data reduction techniques. The best quality $\it{TESS}$-CVZ data, for 5,574 stars where pipelines returned consistent results, provide high quality power spectra across a number of stellar evolutionary states. This makes possible studies of, for example, the Asymptotic Giant Branch bump (AGBb). We demonstrate that mixed $\ell=1$ modes and rotational splitting are cleanly observed in the 1-year data set. By combining $\it{TESS}$-CVZ data with $\it{TESS}$-HERMES, $\it{SkyMapper}$, APOGEE and $\it{Gaia}$ we demonstrate the potential for Galactic archaeology studies using the data, which provides good age precision and accuracy that reproduces the age of high $\mathrm{[\alpha/Fe]}$ stars and relationships between mass and kinematics from studies based on $\it{Kepler}$. Better quality astrometry and simpler target selection than the $\it{Kepler}$ sample makes this data ideal for studies of the local star formation history and evolution of the Galactic disc. These results provide a strong case for detailed spectroscopic follow-up in the CVZs to complement that which has been (or will be) collected by current surveys. [Abridged]Comment: 15 Pages (+6 Pages Appendices), 14 Figures (+3 in Appendices). Re-submitted to MNRAS following positive initial review. Full catalogue with seismic parameters, mass and age estimates available at https://zenodo.org/record/4299142#.X8VseC2ZNN