Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Stau Search in IceCube

The tau lepton’s supersymmetric partner, the stau, appears in some models as the next-to-lightest supersymmetric particle. Their deacy process into the lightest superpartner is usually suppressed by supersymmetry breaking, which makes it a long-lived particle. In this scenario, its signature is a long, minimally ionizing track when traveling through the IceCube detector. Independent of their primary energy, the stau tracks appear like low-energy muons in the detector. A potential signal of staus would thus be an excess over muon tracks induced by atmospheric muon neutrinos. Our analysis focuses on the region around the horizon as here the ratio between stau signal and atmospheric background is largest. We will present the first sensitivity to constrain the stau mass using IceCube and demonstrate the potential of this analysis with future improvements