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T Reich

Publications and source records attributed to T Reich.

At least 19 recordsLinked to original sources

Complexation of uranium(VI) with protocatechuic acid-application of iterative transformation factor analysis to EXAFS spectroscopy.

The speciation of 1 mM uranium(VI) in carbonate-free aqueous solutions of 50 mM protocatechuic acid (PCA, 3,4-dihydroxybenzoic acid) was studied in the pH range of 4.0 to 6.8 using EXAFS spectroscopy. The uranium L(III)-edge EXAFS spectra were analyzed using a newly developed computer algorithm for iterative transformation factor analysis (FA). Two structural different uranium(VI) complexes were observed. The speciation in the pH range of 4.0 to 4.8 is dominated by a 1:2 or 1:3 uranium(VI)/PCA complex with bidentate coordination of the carboxyl group to the uranium(VI) moiety. Already at pH 4.6 significant amounts of a second species are formed. This uranium(VI) species contains two PCA ligands that are bound to the uranium via their neighboring phenolic hydroxyl groups under formation of five-member rings.

Journal Article↗

Integrating sibship data for mapping quantitative trait loci.

Sibship methods have been shown to be more powerful than traditional sib-pair methods in mapping quantative trait loci. We propose a statistical procedure which integrates data on sibships into a so-called 'contrast function', a natural extension of the classical squared sib-pair trait difference proposed by Haseman & Elston (1972). We also develop a combined mean and contrast function which provides more information on linkage compared to the contrast function. Our method is extended to multiple, epistatically interacting trait loci. Monte-Carlo simulations are included to compare the efficiencies of the proposed procedures with some currently used methods. An application of our proposed method is presented using data on alcohol dependence.

Alcoholism↗

Linkage mapping of quantitative trait loci in humans: an overview.

In this article, we provide an overview of the different statistical procedures that have been developed for linkage mapping of quantitative trait loci. We outline the model assumptions, the data requirements and the underlying tests for linkage for the different methods.

Chromosome Mapping↗

Molecular and atomic analysis of uranium complexes formed by three eco-types of Acidithiobacillus ferrooxidans.

A combination of EXAFS, transmission electron microscopy and energy-dispersive X-ray was used to conduct a molecular and atomic analysis of the uranium complexes formed by Acidithiobacillus ferrooxidans. The results demonstrate that this bacterium accumulates uranium as phosphate compounds. We suggest that at toxic levels when the uranium enters the bacterial cells, A. ferrooxidans can detoxify and efflux this metal by a process in which its polyphosphate bodies are involved.

Biodegradation, Environmental↗

Comparison of 3190 alcohol-dependent individuals with and without suicide attempts.

INTRODUCTION: Suicidal behaviors are often seen in alcohol-dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family-based sample of alcoholics. METHODS: Semistructured, detailed interviews were administered to 3190 alcohol-dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol-dependent probands, controls, and their relatives. RESULTS: As determined by both univariate comparison and multivariate logistic regression analysis, alcohol-dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance-induced psychiatric disorders and other substance dependence. First-degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts, even after controlling for additional relevant diagnoses. CONCLUSION: These results support the hypothesis that alcohol-dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions.

Adult↗

EXAFS as a tool for bond-length determination in the environment of heavy atoms.

Single crystal X-ray diffraction measurements are complicated in the presence of heavy atoms. In these cases the structure factors are mainly influenced by the heavy scatterers and the error in determination of atomic coordinates increases for light atoms. The difficulties grow if the unit cell dimensions or the space group symmetry remain uncertain. If the structure model is similar to the correct structure, it is difficult to find an independent criterion for the accuracy of the bond-length determination. We demonstrate that extended X-ray absorption fine structure (EXAFS) spectroscopy is a useful tool for the investigation of local bond lengths in the environment of heavy atoms.

Journal Article↗

Markov chain Monte Carlo linkage analysis of complex quantitative phenotypes.

We report a Markov chain Monte Carlo analysis of the five simulated quantitative traits in Genetic Analysis Workshop 12 using the Loki software. Our objectives were to determine the efficacy of the Markov chain Monte Carlo method and to test a new scoring technique. Our initial blind analysis, on replicate 42 (the "best replicate") successfully detected four out of the five disease loci and found no false positives. A power analysis shows that the software could usually detect 4 of the 10 trait/gene combinations at an empirical point-wise p-value of 1.5 x 10(-4).

Chromosome Mapping↗

Risk domains associated with an adolescent alcohol dependence diagnosis.

AIMS: To determine the contribution of familial, interpersonal, academic and early substance use factors to relative risk for an alcohol dependence (AD) diagnosis in adolescents. METHODS: Information on 619 adolescents and their 390 sets of biological parents was obtained using the adolescent version of the Child Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) and the adult counterpart of this instrument, the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). The C-SSAGA elicits a wide range of environmental, social, and psychiatric diagnostic information. Specific domain scale scores associated with an adolescent AD were computed, and generalized estimating equations (GEE) modeling was used to determine the odds ratio (relative risk) of the specified risk domains for an alcohol dependence diagnosis. FINDINGS: Risk factors for a DSM-III-R AD diagnosis included being at least 16 years of age, as well as negative parent-child interactions, school and personal-related difficulties (including the presence of an externalizing or internalizing DSM-III-R non-alcohol-related diagnosis), and early experimentations with a variety of substances. CONCLUSIONS: An array of familial, interpersonal, academic and early substance use factors were strongly associated with adolescent AD. Given the findings of this study, further research to determine temporal relationships that might influence the onset of adolescent alcohol dependence is warranted.

Adolescent↗

A bootstrapped commingling analysis of platelet monoamine oxidase activity levels corrected for cigarette smoking.

Monoamine oxidase (MAO) activity levels have been suggested as a possible biological marker for alcohol dependence and abuse, as well as for schizophrenia and other psychiatric conditions. Using platelet MAO activities in the Collaborative Study on the Genetics of Alcoholism data set, we applied bootstrapping methods as a novel way to test for admixture in families. This bootstrapping involved resampling in family units and hypothesis testing of the resampled datasets for commingling in the distribution of MAO activity levels. Prior to commingling analysis, we used linear models to find covariates of greatest effect on MAO activity levels. While an alcoholism diagnosis was significant in men (n = 1151, P < 0.0001) and women (n = 1254, P = 0.0003), the effect lost significance after controlling for cigarette smoking, indicating alcoholism and smoking behavior to be highly confounded. When smoking histories were compared, former smokers had levels (mean = 7.1) closer to those who never smoked (mean = 7.0) than to current smokers (mean = 5.4). Furthermore, current daily smoking and time since smoking cessation were significantly related to MAO levels, indicating smoking probably has a direct effect on MAO levels, rather than the reverse. These results suggest that studies using MAO levels as a biological marker should consider smoking as an important covariate. Finally, admixture was found in MAO levels controlled for smoking and sex, possibly indicating a major genetic locus; this confirms previous evidence for admixture.

Biomarkers↗

Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence.

OBJECTIVE: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. METHOD: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. RESULTS: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. CONCLUSIONS: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.

Adolescent↗

Evidence for a locus on chromosome 1 that influences vulnerability to alcoholism and affective disorder.

OBJECTIVE: Depression (major depression or depressive syndrome) is more prevalent in alcoholic than in nonalcoholic subjects in families with multiple members with alcoholism studied as part of the Collaborative Study on the Genetics of Alcoholism (National Institute on Alcohol Abuse and Alcoholism). First-degree relatives of probands with comorbid alcoholism and depression have a higher prevalence of both disorders than relatives of probands with alcoholism alone, and both groups have a higher prevalence than the relatives of comparison subjects selected without regard to psychopathology. Data from the collaborative study were used to test three phenotypes (comorbid alcoholism and depression, alcoholism or depression, and depression) for genetic linkage. METHOD: Genome-wide sibling-pair linkage analyses were performed with the phenotypes comorbid alcoholism and depression, alcoholism or depression, and depression (major depression or depressive syndrome). Analyses were performed in two data sets (initial and replication data sets) from subject groups ascertained with identical criteria, as well as in the combined data set. RESULTS: Peak lod scores on chromosome 1 (near 120 centimorgan) for the alcoholism or depression phenotype were 5.12, 1.52, and 4.66 in the initial, replication, and combined data sets, respectively. The corresponding lod scores on chromosome 2 were 2.79, 0.20, and 3.26; on chromosome 6, they were 3.39, 0.00, and 0.92; and on chromosome 16, they were 3.13, 0.00, and 2.06. Lod scores on chromosome 2 for the comorbid alcoholism and depression phenotype in the three data sets were 0.00, 4.12, and 2.16, respectively. CONCLUSIONS: The results suggest that a gene or genes on chromosome 1 may predispose some individuals to alcoholism and others to depression (which may be alcohol induced). Loci on other chromosomes may also be of interest.

Adult↗

Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

OBJECTIVE: The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women. METHOD: Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up. RESULTS: About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use. CONCLUSIONS: The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.

Adult↗

A genome-wide search for genes that relate to a low level of response to alcohol.

BACKGROUND: The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. METHODS: A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. RESULTS: Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. CONCLUSIONS: These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.

Alcoholism↗

Genetics of event-related brain potentials in response to a semantic priming paradigm in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Results of a genomewide linkage screen are presented for amplitude of the N4 and P3 components of the ERP, measured at 19 scalp locations in response to a semantic priming task for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. N4 and P3 amplitudes in response to three stimuli (nonwords, primed words [i.e., antonyms], and unprimed words) all showed significant heritabilities, the highest being.54. Both N4 and P3 showed significant genetic correlations across stimulus type at a given lead and across leads within a stimulus, indicating shared genetic influences among the traits. There were also substantial genetic correlations between the N4 and P3 amplitudes for a given lead, even across stimulus type. N4 amplitudes showed suggestive evidence of linkage in several chromosomal regions, and P3 amplitudes showed significant evidence of linkage to chromosome 5 and suggestive evidence of linkage to chromosome 4.

Alcoholism↗

A genome screen of maximum number of drinks as an alcoholism phenotype.

The Collaborative Study on the Genetics of Alcoholism (COGA) is a multicenter research program to detect and map susceptibility genes for alcohol dependence and related phenotypes. The measure M of "maximum number of drinks consumed in a 24-hour period" is closely related to alcoholism diagnosis in this dataset and provides a quantitative measure to grade nonalcoholic individuals. Twin studies have shown log(M) to have a heritability of approximately 50%. Genome screens for this trait were performed in two distinct genotyped samples (wave 1 and wave 2), and in the combined sample. MAPMAKER/SIBS was used to carry out Haseman-Elston based regression analyses. On chromosome 4, an unweighted all-pairs multipoint LOD of 2.2 was obtained between D4S2407 and D4S1628 in wave 1; in wave 2, the region flanked by D4S2404 and D4S2407 gave a LOD of 1.5. In the combined sample, the maximal LOD was 3.5 very close to D4S2407. This evidence for linkage is in the region of the alcohol dehydrogenase gene cluster on chromosome 4. These findings on chromosome 4 are consistent with a prior report from COGA in which strictly defined nonalcoholic subjects in wave 1 were analyzed. The present analysis on log(M) allows more individuals to be included and thus is potentially more powerful.

Alcohol Drinking↗

Family-based study of the association of the dopamine D2 receptor gene (DRD2) with habitual smoking.

A recent study showed an association between the dopamine D2 receptor gene (DRD2) and smoking. The purpose of this study was to determine if the familial transmission of smoking is linked to variation at the DRD2 locus in a genetically informative sample. Subjects were identified in alcohol treatment centers and their relatives were recruited for study. All subjects were interviewed to assess alcohol dependence, smoking habits, and psychiatric disorders. Two polymorphisms within the DRD2 gene were analyzed, including the TaqIA polymorphism. The sample consisted of 138 nuclear families with at least one offspring with habitual smoking, and analysis was by the transmission disequilibrium test (TDT), which avoids problems due to population stratification. There was no significant difference in the frequency between DRD2 alleles transmitted and not transmitted to habitual smokers. There also was no evidence for unequal transmission of DRD2 alleles for the phenotypes "ever smoker" or comorbid alcohol dependence and habitual smoking. This study does not support linkage of the DRD2 with smoking.

Chromosome Mapping↗

Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees.

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest uniformly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipolar recurrent depression (UPR). A hierarchical set of definitions of affected status was examined. Under Model I, affected individuals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results of nonparametric linkage analyses of the extended pedigree structure using the program Genehunter Plus. The strongest finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome-wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18-23, 2000

Bipolar Disorder↗