Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

A numerical scheme for pricing american options with transaction costs under a jump diffusion process

In this paper we develop a numerical method for a nonlinear partial integro-differential complementarity problem arising from pricing American options with transaction costs when the underlying assets follow a jump diffusion process. We first approximate the complementarity problem by a nonlinear partial integro-differential equation (PIDE) using a penalty approach. The PIDE is then discretized by a combination of a spatial upwind finite differencing and a fully implicit time stepping scheme. We prove that the coeficient matrix of the system from this scheme is an M-matrix and that the approximate solution converges to the viscosity solution to the PIDE by showing that the scheme is consistent, monotone, and unconditionally stable. We also propose a Newton's iterative method coupled with a Fast Fourier Transform for the computation of the discretized integral term for solving the fully discretized system. Numerical results will be presented to demonstrate the convergence rates and usefulness of this method