Genetic overlap between diagnostic subtypes of ischemic stroke

Background and Purpose: Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Methods: Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. Results: High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10-4) and profile scores (rg=0.72; 95% confid

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Association of common genetic variants with brain microbleeds

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed geno

Critical parameters of superconducting materials and structures

We report here the completion of a one year project to investigate the synthesis, electronic structure, defect structure, and physical transport properties of high temperature superconducting oxide materials. During the course of this project we produced some of the finest samples of single crystal detwinned YBa{sub 2}Cu{sub 3}O{sub 7}, and stoichiometrically perfect (Ba,K)BiO{sub 3}. We deduced the Fermi surface of YBa{sub 2}Cu{sub 3}O{sub 7}, (La,Sr){sub 2}CuO{sub 4}, and (Ba,K)BiO{sub 3} through the recording of the electron momentum density in these materials as measured by positron annihilation spectroscopy and angle resolved photoemission. We also performed extensive studies on Pr substituted (Y,Pr)Ba{sub 2}Cu{sub 3}O{sub 7} so as to further understand the origin of the electron pairing leading to superconductivity