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

Probabilistic Assessment of Bored Pile Wall: A Slope Stabilisation Technique

One of the potential applications of bored piles is the construction of a retaining wall where the piles are closely installed and the spacing between them is often grouted to build a waterproof retaining wall. Based on previous experience, it is observed that the selection of an appropriate retaining structure is crucial to the strength and stability of a structure, provided that the design of retaining structure is adequate and it satisfies the structural requirements. This study considers a Malaysian slope, Bukit Antarabangsa, to perform the probabilistic stability analysis of bored piles. Statistical tools of FORM and Monte Carlo are used to demonstrate the influence of soil parameters on the reliability levels of structure. This paper also presents the load and resistance factors which are developed to counter the rotational and flexural failure modes of a bored pile wall. It is expected that this study will provide a support to the Malaysian geotechnical industry to integrate a reliability-based design for slope construction

Athletes' career transition out of sport: A systematic review

The purpose of this study was to provide a systematic review of studies on athletes' career transition out of sport from 1968 until the end of 2010. A total of 126 studies were evaluated and reported in three sections: sample characteristics, research designs and correlates of athletes' career transition adjustment. Samples ranged from 1 to 1617. Investigators examined a wide range of competitive levels, both genders and various sports. Researchers have used qualitative (44%), quantitative (44%), and mixed-model (12%) designs. Variables correlated to athletes' career transition adjustment were categorized into factors related to career transition (e.g., self-identity) and available resources during the career transition process (e.g., social support). The discussion focuses on the current status of the study area, limitations in its knowledge, suggested practical implications (e.g., providing proactive support) and future research directions (e.g., examining athletes' retirement decision-making process)