Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that ...exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10(-8)) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 x 10(-8)) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10(-9)), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10(-9)) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10(-8))). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood.
We study Josephson-like junctions formed by materials with antiferromagnetic (AF) order parameters. As an antiferromagnet, we consider a two-band material in which a spin density wave (SDW) arises. ...The spin current j sub(Sp) in AF/F/AF junctions with a ballistic ferromagnetic layer and in tunnel AF/I/AF junctions is calculated. It depends on the angle between the magnetization vectors in the AF leads in the same way as the Josephson current depends on the phase difference of the superconducting order parameters in S/I/S tunnel junctions. We also calculate the dependence of j sub(Sp) on the deviation from the ideal nesting in the AF/I/AF junctions. The spin current is maximal in the insulating phase of the AF and decreases in the metallic phase. It turns to zero at the Neel point when the amplitude of the SDW is zero and changes sign for certain values of the detuning parameter.
Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and ...cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 × 10−8; rs944002 in C14orf73 on chromosome 14, P = 4.7 × 10−13; rs340005 in RORA on chromosome 15, P = 2.4 × 10−8), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P
HET = 5.6 × 10−12 at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.
Over the last several hundred years, donkeys have adapted to high-altitude conditions on the Tibetan Plateau. Interestingly, the kiang, a closely related equid species, also inhabits this region. ...Previous reports have demonstrated the importance of specific genes and adaptive introgression in divergent lineages for adaptation to hypoxic conditions on the Tibetan Plateau. Here, we assessed whether donkeys and kiangs adapted to the Tibetan Plateau via the same or different biological pathways and whether adaptive introgression has occurred. We assembled a de novo genome from a kiang individual and analyzed the genomes of five kiangs and 93 donkeys (including 24 from the Tibetan Plateau). Our analyses suggested the existence of a strong hard selective sweep at the EPAS1 locus in kiangs. In Tibetan donkeys, however, another gene, i.e., EGLN1, was likely involved in their adaptation to high altitude. In addition, admixture analysis found no evidence for interspecific gene flow between kiangs and Tibetan donkeys. Our findings indicate that despite the short evolutionary time scale since the arrival of donkeys on the Tibetan Plateau, as well as the existence of a closely related species already adapted to hypoxia, Tibetan donkeys did not acquire adaptation via admixture but instead evolved adaptations via a different biological pathway.
Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with ...personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10(-06), KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.
We present a search for the decays of a neutral scalar boson produced by kaons decaying at rest, in the context of the Higgs portal model, using the MicroBooNE detector. We analyze data triggered in ...time with the Fermilab NuMI neutrino beam spill, with an exposure of 1020 protons on target. We look for monoenergetic scalars that come from the direction of the NuMI hadron absorber, at a distance of 100 m from the detector, and decay to electron-positron pairs. We observe one candidate event, with a standard model background prediction of 1.9±0.8. We set an upper limit on the scalar–Higgs mixing angle of θ<(3.3−4.6)×10−4 at the 95% confidence level for scalar boson masses in the range(100–200) MeV/c2. We exclude, at the 95% confidence level, the remaining model parameters required to explain the central value of a possible excess of KL0→π0νν¯ decays reported by the KOTO collaboration. We also provide a model-independent limit on a new boson X produced in K→πX decays and decaying to e+e−.
This study analyzes the potential and consequences of Washington State's use of wind, water, and sunlight (WWS) to produce electricity and electrolytic hydrogen for 100% of its all-purposes energy ...(electricity, transportation, heating/cooling, industry) by 2050, with 80–85% conversion by 2030. Electrification plus modest efficiency measures can reduce Washington State's 2050 end-use power demand by ∼39.9%, with ∼80% of the reduction due to electrification, and can stabilize energy prices since WWS fuel costs are zero. The remaining demand can be met, in one scenario, with ∼35% onshore wind, ∼13% offshore wind, ∼10.73% utility-scale PV, ∼2.9% residential PV, ∼1.5% commercial/government PV, ∼0.65% geothermal, ∼0.5% wave, ∼0.3% tidal, and ∼35.42% hydropower. Converting will require only 0.08% of the state's land for new footprint and ∼2% for spacing between new wind turbines (spacing that can be used for multiple purposes). It will further result in each person in the state saving ∼$85/yr in direct energy costs and ∼$950/yr in health costs eliminating ∼830 (190–1950)/yr statewide premature air pollution mortalities while reducing global climate costs by ∼$4200/person/yr (all in 2013 dollars). Converting will therefore improve health and climate while reducing costs.
•Plan to power Washington State's all-purpose energy with wind, water, sunlight (WWS).•Convert 80–85% of existing energy to WWS by 2030 and 100% by 2050.•Electrification reduces power demand by ∼39.9%, and WWS stabilizes energy prices.•Each person saves ∼$85/yr energy, ∼$950/yr health, $4 200/yr global climate.•New land footprint <0.08% of state; spacing <2% and usable for multiple purposes.
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