Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10−7≤P≤1.1*10−5) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10−6). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10−4) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans

SYSTEM FOR VELOCITY RATIO MEASUREMENTS OF AN AXIS-ROTATING ELECTRON-BEAM

A novel system to measure the ratio of transverse velocity to axial velocity (alpha) of a low voltage, axis-rotating electron beam is described herein. With the system, more information about the beam can be obtained than from the usual slit/phosphor screen system. Since most of the beam is undisturbed before the phosphor screen, the beam radius and azimuthal symmetry can be quantified in combination with the beam alpha along various axial positions. The diagnostic is applied to a Cusptron microwave tube to measure these electron beam parameters which are important for high tube efficiency. Two magnetic field profiles are used to study various causes of low beam quality, while a third profile is used in attempt to maintain a high quality beam. By using the described system, it is shown that the third profile significantly increases beam quality. The system can easily be extended to higher energy beams with an appropriate scintillator.open110sciescopu