Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A)

Stick-Slip Tremor Beneath an Alpine Glacier

Sliding of glacial ice over its base is typically described by a frictionless or slowly deforming bed. This view is challenged by recent seismic observations of stick-slip motion at the icebed interface. We revisit a high-frequency (20–35 Hz) harmonic tremor recorded on Gornergletscher, Switzerland. In contrast to previous interpretation in terms of glaciohydraulic tremor, we present evidence for superimposed stick-slip episodes as tremor sources: we locate the tremor source with matched field processing polarity optimization, which allows for azimuthal polarity patterns associated with nonisotropic moment tensors and yields a tremor source clustering near the glacier bed. Our analysis confirms an S wave radiation pattern in agreement with a double-couple source derived from ice sliding over bedrock and explains our tremor observations in terms of glacier stick-slip motion. Adding to observations of stick-slip tremor beneath polar ice streams, this first report on stick-slip tremor beneath Alpine ice favors widespread seismogenic glacier sliding