28 research outputs found
GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment
Recommended from our members
Computerized Tomography, Diagnostic Ultrasound, and Radionuclide Scanning: Comparison of Efficacy in Diagnosis of Pancreatic Carcinoma
Forty-six patients, including 33 with proved pancreatic carcinoma, were studied with computerized tomography (CT), ultrasound (US), and radionuclide (RN) scanning. The results of each scanning procedure were compared with the surgical and clinical findings. The detection rate was 82% for CT, and 92% with US. A mass is the most important finding in the diagnosis of pancreatic carcinoma. Measurements of the pancreas with CT and US were similar, with visualization of all parts of the pancreas routinely better with CT scans. Radionuclide scans were abnormal in 96% of the patients with pancreatic carcinoma as well as in 75% of patients without pancreatic disease. A rational approach to examination of a patient with suspected pancreatic carcinoma should begin with US scan when available, because the detection rate with this method is equal to that with CT and its cost per procedure and for equipment is substantially less.(JAMA 238:2040-2042, 1977