Magnetic impurity coupled to interacting conduction electrons

We consider a magnetic impurity which interacts by hybridization with a system of weakly correlated electrons and determine the energy of the ground state by means of an 1/N_f expansion. The correlations among the conduction electrons are described by a Hubbard Hamiltonian and are treated to lowest order in the interaction strength. We find that their effect on the Kondo temperature, T_K, in the Kondo limit is twofold: First, the position of the impurity level is shifted due to the reduction of charge fluctuations, which reduces T_K. Secondly, the bare Kondo exchange coupling is enhanced as spin fluctuations are enlarged. In total, T_K increases. Both corrections require intermediate states beyond the standard Varma-Yafet ansatz. This shows that the Hubbard interaction does not just provide quasiparticles, which hybridize with the impurity, but also renormalizes the Kondo coupling.Comment: ReVTeX 19 pages, 3 uuenconded postscript figure

The Kondo lattice model with correlated conduction electrons

We investigate a Kondo lattice model with correlated conduction electrons. Within dynamical mean-field theory the model maps onto an impurity model where the host has to be determined self-consistently. This impurity model can be derived from an Anderson-Hubbard model both by equating the low-energy excitations of the impurity and by a canonical transformation. On the level of dynamical mean-field theory this establishes the connection of the two lattice models. The impurity model is studied numerically by an extension of the non-crossing approximation to a two-orbital impurity. We find that with decreasing temperature the conduction electrons first form quasiparticles unaffected by the presence of the lattice of localized spins. Then, reducing the temperature further, the particle-hole symmetric model turns into an insulator. The quasiparticle peak in the one-particle spectral density splits and a gap opens. The size of the gap increases when the correlations of the conduction electrons become stronger. These findings are similar to the behavior of the Anderson-Hubbard model within dynamical mean-field theory and are obtained with much less numerical effort.Comment: 7 pages RevTeX with 3 ps figures, accepted by PR

Periodic Anderson model with correlated conduction electrons

We investigate a periodic Anderson model with interacting conduction electrons which are described by a Hubbard-type interaction of strength U_c. Within dynamical mean-field theory the total Hamiltonian is mapped onto an impurity model, which is solved by an extended non-crossing approximation. We consider the particle-hole symmetric case at half-filling. Similar to the case U_c=0, the low-energy behavior of the conduction electrons at high temperatures is essentially unaffected by the f-electrons and for small U_c a quasiparticle peak corresponding to the Hubbard model evolves first. These quasiparticles screen the f-moments when the temperature is reduced further, and the system turns into an insulator with a tiny gap and flat bands. The formation of the quasiparticle peak is impeded by increasing either U_c or the c-f hybridization. Nevertheless almost dispersionless bands emerge at low temperature with an increased gap, even in the case of initially insulating host electrons. The size of the gap in the one-particle spectral density at low temperatures provides an estimate for the low-energy scale and increases as U_c increases.Comment: 11 pages RevTeX with 13 ps figures, accepted by PR

Interaction of a Magnetic Impurity with Strongly Correlated Conduction Electrons

We consider a magnetic impurity which interacts by hybridization with a system of strongly correlated conduction electrons. The latter are described by a Hubbard Hamiltonian. By means of a canconical transformation the charge degrees of freedom of the magnetic impurity are eliminated. The resulting effective Hamiltonian $H_{\rm eff}$ is investigated and various limiting cases are considered. If the Hubbard interaction $U$ between the conduction electrons is neglected $H_{\rm eff}$ reduces to a form obtained by the Schrieffer-Wolff transformation, which is essentially the Kondo Hamiltonian. If $U$ is large and the correlations are strong $H_{\rm eff}$ is changed. One modification concerns the coefficient of the dominant exchange coupling of the magnetic impurity with the nearest lattice site. When the system is hole doped, there is also an antiferromagnetic coupling to the nearest neighbors of that site involving additionally a hole. Furthermore, it is found that the magnetic impurity attracts a hole. In the case of electron doping, double occupancies are repelled by the impurity. In contrast to the hole-doped case, we find no magnetic coupling which additionally involves a doubly occupied site.Comment: 16 pages, Revtex 3.

Multi-center genetic study of hypertension: The Family blood pressure program (FBPP)

The Family Blood Pressure Program (FBPP) consists of 4 independently established multicenter networks of investigators who have complementary approaches to the genetics of blood pressure levels and hypertension. The program has recruited participants from the African American, Mexican American, Asian, and non-Hispanic white populations. Each network utilized study designs, laboratory measurements, and analytic methods that made efficient use of the unique characteristics of their populations and the investigators expertise. The individual networks subsequently unified core study components into a single cohesive program. The unified FBPP includes (1) standardized clinic and laboratory protocols for core variables to facilitate direct comparison of results among networks, (2) coordination among laboratories to avoid unnecessary duplication of effort, (3) utilization of a single laboratory for genome-wide marker typing, and (4) a pooled data set containing phenotype and genotype information from \u3e 11 000 individuals

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health

Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR

Loci influencing blood pressure identified using a cardiovascular gene-centric array

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.</p

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease