Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Recent progress in L-H transition studies at JET: Tritium, Helium, Hydrogen and Deuterium

We present an overview of results from a series of L-II transition experiments undertaken at JET since the installation of the ITER-like-wall (JET-ILW), with beryllium wall tiles and a tungsten divertor. Tritium, helium and deuterium plasmas have been investigated. Initial results in tritium show ohmic L-H transitions at low density and the power threshold for the L-H transition (P-LH) is lower in tritium plasmas than in deuterium ones at low densities, while we still lack contrasted data to provide a scaling at high densities. In helium plasmas there is a notable shift of the density at which the power threshold is minimum ((n) over bar (e,min)) to higher values relative to deuterium and hydrogen references. Above (n) over bar (e,min) (He) the L-H power threshold at high densities is similar for D and He plasmas. Transport modelling in slab geometry shows that in helium neoclassical transport competes with interchange-driven transport, unlike in hydrogen isotopes. Measurements of the radial electric field in deuterium plasmas show that E-r shear is not a good indicator of proximity to the L-H transition. Transport analysis of ion heat flux in deuterium plasmas show a non-linearity as density is decreased below (n) over bar (e,min). Lastly, a regression of the JET-ILW deuterium data is compared to the 2008 ITPA scaling law