Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine

Measurement of internal jet structure in dijet production in deep inelastic scattering at HERA

Internal jet structure in dijet production in deep-inelastic scattering is measured with the H1 detector at HERA. Jets with transverse energies ET,Breit > 5 GeV are selected in the Breit frame employing k_perp and cone jet algorithms. In the kinematic region of squared momentum transfers 10 < Q2 <~ 120 GeV2 and x-Bjorken values 2.10^-4 <~ xBj <~ 8.10^-3, jet shapes and subjet multiplicities are measured as a function of a resolution parameter. Distributions of both observables are corrected for detector effects and presented as functions of the transverse jet energy and jet pseudo-rapidity. Dependences of the jet shape and the average number of subjets on the transverse energy and the pseudo-rapidity of the jet are observed. With increasing transverse jet energies and decreasing pseudo-rapidities, i.e.towards the photon hemisphere, the jets are more collimated. QCD models give a fair description of the data.Comment: 18 pages, 6 figures, submitted to Nucl. Phys.