Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10−8) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10−12), CD28 (rs6435203, p=1.35×10−9), LPP (rs4686953, p=3.35×10−8), ETS1 (rs3809006, p=7.74×10−9), DLEU1 (rs806349, p=8.14×10−12), LPIN3 (rs6072343, p=7.16×10−12) and IFNGR2 (rs9808753, p=4.40×10−10). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses

Electron paramagnetic resonance study of the multisite character of Yb3+ ions in LuVO4 single crystals

Electron paramagnetic resonance (EPR) is used to identify the different substitution sites of Yb3+ ions in the LuVO4 host. Three different types of sites are observed. One site, referred to as YbI, with tetragonal D2d symmetry characterized by g-values of and , corresponds to 80% (50%) of the total number of Yb3+ ions for the 1% (5%) doped compound. Two other tetragonal sites, referred to as YbII a,II b, with the same D2d symmetry and characterized by g-values of , and , , represent 20% (50%) of the total number of ytterbium ions for the 1% (5%) compound. One minor site, referred to as YbIII, corresponding to less than 1% of the Yb3+ ions, with a lower C2v or D2 symmetry, is also seen in the EPR spectra. The temperature dependence of the EPR linewidth is studied and shows for all the sites a dominant Orbach process for the spin-lattice relaxation time T1 for T>12 K

Single-frequency operation of an orange avalanche upconversion laser for high-resolution laser spectroscopy

We report single transverse and longitudinal mode operation of an all solid-state orange laser pumped at 821 nm. Oscillation at 607 nm by avalanche upconversion in Pr, Yb: BaY(2)F(8) pumped by a Ti-Sapphire laser at 821 nm is obtained with a threshold as low as 570 mW. A maximum output power of 12 mW is obtained for a pump power of 2.5 W

Hyperfine structure, optical dephasing, and spectral-hole lifetime of single-crystalline Pr3+: La-2(WO4)(3)

Most of the experiments related to quantum information applications, involving rare-earth doped inorganic crystals, are performed on yttrium orthosilicate single crystals. The work presented here is motivated by the search of new compounds which can be used in the field of quantum computing and/or quantum storage. Relaxation times and hyperfine structure of the H-3(4)(0)-> D-1(2)(0) transition in 1.4% Pr3+:La-2(WO4)(3) at 4 K have been measured by photon-echo and spectral-hole-burning techniques. The hyperfine splittings of the ground H-3(4)(0) and the excited D-1(2)(0) states are 14.9 +/- 0.1 MHz, 24.6 +/- 0.1 MHz and 5.0 +/- 0.1 MHz, 7.3 +/- 0.1 MHz, respectively. An inhomogeneous linewidth of 18.8 +/- 0.1 GHz was measured. A homogeneous linewidth of 25.3 +/- 2.0 kHz was obtained with or without an external magnetic field of about 14 mT. The fluorescence dynamics of the D-1(2) level obtained by a direct excitation in the H-3(4)-> D-1(2) transition gives a nonexponential decay which indicates energy-transfer processes. This decay can be accurately fitted by the Inokuti-Hirayama model [J. Chem. Phys. 43, 1978 (1965)] with a radiative lifetime of 61 +/- 1 mu s giving a minimal homogeneous linewidth of 2.6 kHz. The spectral-hole lifetime due to population redistribution within the ground hyperfine levels is 16 +/- 2 s. The results obtained for the La-2(WO4)(3) compound make this crystal an interesting host for quantum applications

Linear and non-linear spectroscopy of Ho3+-doped YVO4 and LuVO4

Rare-earth-doped crystals can be attractive materials for quantum information processing, because of the long coherence times that can be expected, in particular, from non-Kramers ions. In this paper, Ho3+-doped yttrium and lutetium vanadate single crystals have been investigated using linear and coherent optical spectroscopy. For Ho3+:YVO4, the crystal-field levels of the I-5(8), F-5, F-5(4) and S-5(2) multiplets have been determined and compared with crystal-field level calculations. This allowed us to unambiguously assign most of the observed transitions, although some results suggest that the site symmetry of the Ho3+ ion could deviate from D-2d. Similar conclusions were reached for Ho3+:LuVO4. Hole burning measurements indicate that the coherence time of the I-5(8)-F-5(5) optical transitions is rather short in both compounds (around 40 ns). Assuming that the coherence is limited by spin interactions, this is accounted for by the high nuclear moment of the nearby vanadium ions, since the large crystal-field level splittings of the I-5(8) and F-5(5) multiplets do not favour a large enhanced nuclear Zeeman effect

Linear and non-linear spectroscopy of Ho3+-doped YVO4 and LuVO4

Rare-earth-doped crystals can be attractive materials for quantum information processing, because of the long coherence times that can be expected, in particular, from non-Kramers ions. In this paper, Ho3+-doped yttrium and lutetium vanadate single crystals have been investigated using linear and coherent optical spectroscopy. For Ho3+:YVO4, the crystal-field levels of the I-5(8), F-5, F-5(4) and S-5(2) multiplets have been determined and compared with crystal-field level calculations. This allowed us to unambiguously assign most of the observed transitions, although some results suggest that the site symmetry of the Ho3+ ion could deviate from D-2d. Similar conclusions were reached for Ho3+:LuVO4. Hole burning measurements indicate that the coherence time of the I-5(8)-F-5(5) optical transitions is rather short in both compounds (around 40 ns). Assuming that the coherence is limited by spin interactions, this is accounted for by the high nuclear moment of the nearby vanadium ions, since the large crystal-field level splittings of the I-5(8) and F-5(5) multiplets do not favour a large enhanced nuclear Zeeman effect

Hyperfine structure and hyperfine coherent properties of praseodymium in single-crystalline La-2(WO4)(3) by hole-burning and photon-echo techniques

We studied the hyperfine structure and hyperfine coherent properties of the H-3(4)(0)-> D-1(2)(0) transition of Pr3+ ions in a tungstate single crystal La-2(WO4)(3) by hole-burning and photon-echo techniques. This work is motivated by the search of an efficient three level Lambda system in this new compound with which we could build up a quantum memory. By nonconventional hole-burning experiments, the ordering of the hyperfine splittings in the H-3(4)(0) ground state and in the D-1(2)(0) excited state is obtained. The hyperfine splittings are thus ordered: 24.6 and 14.9 MHz for the H-3(4)(0) level and 5.0 and 7.3 MHz for the D-1(2)(0) level. The relative and absolute transition strengths of individual hyperfine transitions are determined by comparing absorption strengths and by measuring the Rabi flopping frequency as the transition is coherently driven. Free induction and Raman echo decays give inhomogeneous and homogeneous hyperfine linewidths of 57 +/- 2 and 1.25 +/- 0.1 kHz, respectively