CHRNA5 and CHRNA3 variants and level of neuroticism in young adult Mexican American men and women

A lifetime history of alcohol dependence has been associated with elevations in neuroticism in Mexican American young adults. The identification of genetic markers associated with neuroticism and their influence on the development of alcohol use disorders (AUD) may contribute to our understanding of the relationship between personality traits and the increased risk of AUD in Mexican Americans. The purpose of this study was to investigate associations between neuroticism and 13 single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine (nAChR) α5-subunit (CHRNA5) and α3-subunit (CHRNA3) genes in young adult Mexican American men and women. Participants were four hundred sixty-five young adult Mexican American men and women who are literate in English and are residing legally in San Diego County. Each participant gave a blood sample and completed a structured diagnostic interview. Neuroticism was assessed using the Maudsley Personality Inventory. The minor alleles of four CHRNA5 polymorphisms (rs588765, rs601079, rs680244 and rs555018) and three CHRNA3 polymorphisms (rs578776, rs6495307 and rs3743078) showed associations with neuroticism. Several of these SNPs also displayed nominal associations with DSM-IV alcohol and nicotine dependence, but tests of mediation suggested that these relations could be partially explained by the presence of co-occurring neuroticism. These findings suggest that genetic variations in nicotinic receptor genes may influence the development of neuroticism, which in turn is involved in the development of AUDs and nicotine dependence in Mexican American young adults

Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population

Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample

Single nucleotide polymorphisms in the REG-CTNNA2 region of chromosome 2 and NEIL3 associated with impulsivity in a Native American sample: LCWGS for impulsivity in an American Indian community

Impulsivity is a multi-faceted construct that, while characterized by a set of correlated dimensions, is centered around a core definition that involves acting suddenly in an unplanned manner without consideration for the consequences of such behavior. Several psychiatric disorders include impulsivity as a criterion, and thus it has been suggested that it may link a number of different behavioral disorders, including substance abuse. Native Americans (NA) experience some of the highest rates of substance abuse of all the US ethnic groups. The described analyses used data from a low-coverage whole genome sequence scan to conduct a genome-wide association study (GWAS) of an impulsivity phenotype in an American Indian community sample (n = 658). Demographic and clinical information were obtained using a semi-structured interview. Impulsivity was assessed using a scale derived from the Maudsley personality inventory that combines both novelty seeking and lack of planning items. The impulsivity score was tested for association with each variant adjusted for demographic variables, and corrected for ancestry and kinship, using emmax. Simulations were conducted to calculate empirical P-values. Genome-wide significant findings were observed for a variant 50-kb upstream from catenin cadherin-associated protein, alpha 2 (CTNNA2), a neuronal-specific catenin, in the REG gene cluster. A meta-analysis of GWAS had previously identified common variants in CTNNA2 as being associated with excitement seeking. A second locus upstream of nei endonuclease VIII-like 3 (NEIL3) on chromosome 4 also achieved genome-wide significance. The association between sequence variants in these regions suggests their potential roles in the genetic regulation of this phenotype in this population

Enhancement effect of bimetallic amide K2Mn(NH2)4 and in-situ formed KH and Mn4N on the dehydrogenation/hydrogenation properties of Li–Mg–N–H system

In this work, we investigated the influence of the K2Mn(NH2)4 additive on the hydrogen sorption properties of the Mg(NH2)2 + 2LiH (Li–Mg–N–H) system. The addition of 5 mol% of K2Mn(NH2)4 to the Li–Mg–N–H system leads to a decrease of the dehydrogenation peak temperature from 200 ◦C to 172 ◦C compared to the pristine sample. This sample exhibits a constant hydrogen storage capacity of 4.2 wt.% over 25 dehydrogenation/rehydrogenation cycles. Besides that, the in-situ synchrotron powder X-ray diffraction analysis performed on the as prepared Mg(NH2)2 + 2LiH containing K2Mn(NH2)4 indicates the presence of Mn4N. However, no crystalline K-containing phases were detected. Upon dehydrogenation, the formation of KH is observed. The presence of KH and Mn4N positively influences the hydrogen sorption properties of this system, especially at the later stage of rehydrogenation. Under the applied conditions, hydrogenation of the last 1 wt.% takes place in only 2 min. This feature is preserved in the following three cycles.Fil: Gizer, Gökhan. Helmholtz zentrum Geesthacht; AlemaniaFil: Cao, Hujun. Helmholtz zentrum Geesthacht; Alemania. Chinese Academy of Sciences; República de ChinaFil: Puszkiel, Julián Atilio. Helmholtz zentrum Geesthacht; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Pistidda, Claudio. Helmholtz zentrum Geesthacht; AlemaniaFil: Santoru, Antonio. Helmholtz zentrum Geesthacht; AlemaniaFil: Zhang, Weijin. Chinese Academy of Sciences; República de ChinaFil: He, Teng. Chinese Academy of Sciences; República de ChinaFil: Chen, Ping. Chinese Academy of Sciences; República de ChinaFil: Klassen, Thomas. Helmholtz zentrum Geesthacht; Alemania. Helmut Schmidt Universität; ArgentinaFil: Dornheim, Martin. Helmholtz zentrum Geesthacht; Alemani

Efficient synthesis of alkali borohydrides from mechanochemical reduction of borates using magnesium-aluminum-basedwaste

Lithium borohydride (LiBH4) and sodium borohydride (NaBH4) were synthesized via mechanical milling of LiBO2, and NaBO2 with Mg-Al-based waste under controlled gaseous atmosphere conditions. Following this approach, the results herein presented indicate that LiBH4 and NaBH4 can be formed with a high conversion yield starting from the anhydrous borates under 70 bar H2. Interestingly, NaBH4 can also be obtained with a high conversion yield by milling NaBO2·4H2O and Mg-Al-based waste under an argon atmosphere. Under optimized molar ratios of the starting materials and milling parameters, NaBH4 and LiBH4 were obtained with conversion ratios higher than 99.5%. Based on the collected experimental results, the influence of the milling energy and the correlation with the final yields were also discussed.Fil: Le, Thi Thu. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; AlemaniaFil: Pistidda, Claudio. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; AlemaniaFil: Puszkiel, Julián Atilio. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; Alemania. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Milanese, Chiara. Universita Degli Studi Di Pavia; ItaliaFil: Garroni, Sebastiano. University of Sassari; ItaliaFil: Emmler, Thomas. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; AlemaniaFil: Capurso, Giovanni. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; AlemaniaFil: Gizer, Gökhan. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; AlemaniaFil: Klassen, Thomas. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; Alemania. Helmut Schmidt University; Alemania. University of the Federal Armed Forces Hamburg; AlemaniaFil: Dornheim, Martin. Helmholtz Zentrum Geesthacht GmbH. Institute of Materials Research, Materials Technology; Alemani

EEG alpha phenotypes: linkage analysis and relation to alcohol dependence in an American Indian community study

Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz) frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may represent an important endophenotype associated with alcohol and other substance dependence

EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study

Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz) frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may represent an important endophenotype associated with alcohol and other substance dependence

Dynamics of porous and amorphous magnesium borohydride to understand solid state Mg-ion-conductors

Rechargeable solid-state magnesium batteries are considered for high energy density storage and usage in mobile applications as well as to store energy from intermittent energy sources, triggering intense research for suitable electrode and electrolyte materials. Recently, magnesium borohydride, Mg(BH$_{4}$)$_{2}$, was found to be an effective precursor for solid-state Mg-ion conductors. During the mechanochemical synthesis of these Mg-ion conductors, amorphous Mg(BH$_{4}$)$_{2}$ is typically formed and it was postulated that this amorphous phase promotes the conductivity. Here, electrochemical impedance spectroscopy of as-received γ-Mg(BH$_{4}$)$_{2}$ and ball milled, amorphous Mg(BH$_{4}$)$_{2}$ confirmed that the conductivity of the latter is ~2 orders of magnitude higher than in as-received γ-Mg(BH$_{4}$)$_{2}$ at 353 K. Pair distribution function (PDF) analysis of the local structure shows striking similarities up to a length scale of 5.1 Å, suggesting similar conduction pathways in both the crystalline and amorphous sample. Up to 12.27 Å the PDF indicates that a 3D net of interpenetrating channels might still be present in the amorphous phase although less ordered compared to the as-received γ-phase. However, quasi elastic neutron scattering experiments (QENS) were used to study the rotational mobility of the [BH$_{4}$] units, revealing a much larger fraction of activated [BH$_{4}$] rotations in amorphous Mg(BH$_{4}$)$_{2}$. These findings suggest that the conduction process in amorphous Mg(BH$_{4}$)$_{2}$ is supported by stronger rotational mobility, which is proposed to be the so-called “paddle-wheel” mechanism

Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of “craving” and “withdrawal” using a family study design. Participants were 2524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis, however, linkage analyses of cannabis “craving” and the cannabis withdrawal symptom of “nervous, tense, restless or irritable” revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes

Genome-wide scan for self-rating of the effects of alcohol (SRE) in American Indians

This study’s aims were to map loci linked to self-rating of the effects of alcohol and to determine if there was overlap with loci previously mapped for other substance dependence phenotypes in an American Indian community at high risk for substance dependence