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

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.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.Clinical epidemiolog

Direct utilization of geothermal energy for space and water heating at marlin texas final report

The Torbett-Hutchings-Smith Memorial Hospital geothermal heating project, which is one of nineteen direct-use geothermal projects funded principally by DOE, is documented. The five-year project encompassed a broad range of technical, institutional, and economic activities including: resource and environmental assessments; well drilling and completion; system design, construction, and monitoring; economic analyses; public awareness programs; materials testing; and environmental monitoring. Some of the project conclusions are that: (1) the 155/sup 0/F Central Texas geothermal resource can support additional geothermal development; (2) private-sector economic incentives currently exist, especially for profit-making organizations, to develop and use this geothermal resource; (3) potential uses for this geothermal resource include water and space heating, poultry dressing, natural cheese making, fruit and vegetable dehydrating, soft-drink bottling, synthetic-rubber manufacturing, and furniture manufacturing; (4) high maintenance costs arising from the geofluid's scaling and corrosion tendencies can be avoided through proper analysis and design; (5) a production system which uses a variable-frequency drive system to control production rate is an attractive means of conserving parasitic pumping power, controlling production rate to match heating demand, conserving the geothermal resource, and minimizing environmental impacts. Document type: Repor