bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcoholism as a complex trait: Comparison of genetic models and role of epidemiological risk factors
Authors: Macciardi Fabio , Morenghi Emanuela , Morabito Alberto 
Published: November 2013

AbstractA genetic component for alcoholism appears likely, but the genes involved have yet to be identified. The mode of inheritance is probably more complex than for traditional mendelian disorders. In particular, there are marked differences in alcoholism by gender, parent‐of‐origin effects, ethnicity, and other epidemiological factors. We investigated the evidence for the presence of susceptibility genes for alcohol dependence in the Collaborative Study on the Genetics of Alcoholism data set.
Linkage of chromosome 1 markers to alcoholism‐related phenotypes by sib pair linkage analysis of principal components
Authors: Olson Jane M. , Rao Shaoqi , Jacobs Kevin , Elston Robert C. 
Published: November 2013

AbstractUsing the Collaborative Study on the Genetics of Alcoholism data and affected‐sib‐pair linkage methods, Reich et al. [1998] reported linkage of alcohol dependence to a region near D1S1588 on chromosome 1. In this paper, we assessed the ability of multivariate sib‐pair linkage analysis of the neurophysiologic measurements (including age and sex) to evaluate evidence for linkage to chromosome 1. Principal components of 16 neurophysiologic measurements, plus age and sex, were analyzed separately using sib‐pair linkage analysis, and a cumulative sum of the resulting r‐statistics computed at each point on the chromosome. The first four principal components, which accounted for 74% of the total variation, showed little or no evidence for linkage in the D1S1588 region, while the remaining components showed substantial evidence for linkage. We conclude that potentially important linkage results can be missed if investigators limit attention only to major sources of variability.
Genome scans for genetic predisposition to alcoholism by use of transmission disequilibrium test analyses
Authors: Page Grier P. , King Terri M. , Barnholtz Jill S. , Andrade Mariza De , Peterson Leif E. , Amos Christopher I. 
Published: November 2013

AbstractWe report the results of the analysis of three measures of alcoholism and six associated symptoms using transmission disequilibrium (TDT) analysis on data from the Collaborative Study on the Genetics of Alcoholism data set. Implementation of identity‐by‐state (IBS) routines for error checking revealed 10 reported full siblings that were rejected as a full sibling to all of their purported full siblings with p < 0.05. TDT analysis revealed two loci with significant transmission disequilibrium (p < 0.001) on chromosomes 1 and 7. Analysis by parental origin found alleles at three loci displaying significant disequilibrium in the transmission of the paternal alleles for at least three of the nine tested traits. These loci are on chromosomes 6, 9, and 13. Analyses of Caucasian families alone and the use of a single affected individual from each family also yielded significant results for the loci on chromosomes 6, 9, and 13.
Genome‐wide linkage analysis using genetic variance components of alcohol dependency‐associated censored and continuous traits
Authors: Palmer Lyle J. , Tiller Katrina J. , Burton Paul R. 
Published: November 2013

AbstractWe used variance‐components analysis to investigate the additive genetic effects regulating some of the phenotypes included in the GAW11 data set. Variance‐components models were fitted using Gibbs sampling methods in BUGS v 0.6. Linkage analyses for both multivariate normal (MvN) traits and right censored survival times (age‐of‐onset) were based upon standard Haseman‐Elston identity‐by‐descent sib‐pair methods applied directly to traits showing evidence of substantial additive genetic determination (residualized for any important covariates) and to the estimated σ2∧residuals for those traits. Harm avoidance behavior (TPQ subscale) showed evidence of linkage to markers on chromosomes 1, 13, and 18. P300 levels at the Fp1 site showed evidence of linkage to markers on chromosomes 2, 3, 9, 12, 17, 19, and 20. Platelet monoamine oxidase B (MAOB) levels showed evidence of linkage to D4S1651. The age‐of‐onset for ALDX1 in those over 30 years old showed evidence of linkage to markers on chromosomes 1, 6, 14, and 15. The age‐of‐onset for the more strictly defined ALDX2 in those over 30 years old showed evidence of linkage to markers on chromosomes 7 and 14. These results are consistent with a complex, multifactorial susceptibility to alcohol dependency.
Analyses of the COGA data set in one ethnic group with examinations of alternative definitions of alcoholism
Authors: Sheffield L.J. , Knauert M.P. , Pakstis A.J. , Zhao H. , Kidd K.K. 
Published: November 2013

AbstractWe used GENEHUNTER and GENEHUNTER‐PLUS to search for linkage with the markers in the Collaborative Study on the Genetics of Alcoholism (COGA) data set in a single ethnic group. Analyses of a complex disorder such as alcoholism depend on the definition of affection status. The COGA study provides two definitions of alcoholism (variables ALDX1 and ALDX2). To identify more severely affected alcoholics that might be more homogeneous genetically, we developed two other ways of characterizing subjects as alcohol dependent: (1) by combining the symptom variable values equally into a 24‐point scale and (2) by weighting optimally the symptoms and other descriptive variables into a single score using logistic regression. We applied these definitions within a single ethnic group to map alcoholism‐related loci. We found two regions on chromosome 1 that have adjacent markers significant at p‐values ≤ 0.05. ALDX1 provided the highest Z‐scores compared to the alternatives.
Effects of genotype×sex interaction on linkage analysis of visual event‐related evoked potentials
Authors: Towne Bradford , Almasy Laura , Siervogel Roger M. , Blangero John 
Published: November 2013

AbstractAutosomal genes contributing to variation in many complex traits are influenced by male or female physiological “environments.” Accounting for such genotype‐by‐sex (G×S) interactions has been shown to be important in quantitative genetic, segregation, and linkage analyses of a number of sexually dimorphic traits. In analyses of data simulated for GAW10, we showed that incorporating sex‐specific variance components into a variance components‐based linkage method increased the power to detect linkage in a trait that exhibited G×S interaction. The goals of this study of data from the Collaborative Study on the Genetics of Alcoholism (COGA) were to screen the event‐related brain potential (ERP) data from COGA participants for G×S interaction, and then to conduct variance components linkage analysis of ERP phenotypes showing evidence of G×S interaction using models incorporating sex‐specific variance components. Significant G×S interaction was found in four ERP phenotypes: N100 measured at occipital leads 1 and 2, and P300 measured at occipital leads 1 and 2. In linkage analyses of these traits, the most significant lod score found was that between N100 occipital lead 1 amplitude and marker D7S490. The peak lod score at the D7S490 locus was 2.45 without sex‐specific variance components, and 3.25 with sex‐specific marker and residual polygenic components.
Evidence for linkage and association to alcohol dependence on chromosome 19
Authors: Valdes Ana M. , McWeeney Shannon K. , Thomson Glenys 
Published: November 2013

AbstractAn association study on markers showing suggestive evidence for linkage to severe alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism (COGA) data set. Our linkage study was restricted to the autosomal markers on chromosomes 2, 3, 4, 13, and 19, with low homozygosity (below 30%) and high identity‐by‐state sharing in affected sib pairs (ASPs). We used a strict phenotype definition, only individuals diagnosed as affected both on the ALDX1 (COGA criterion) and ALDX2 (ICD‐10) scales were used in the analyses. Linkage was assessed by excess identity‐by‐descent allele sharing in ASPs. The strongest evidence of linkage was detected on chromosome 19, in particular at markers D19S49 (p < 0.0001) and D19S431 (p < 0.002). An association study of allele and haplotype data was then carried out on chromosome 19 markers using affected‐family‐based controls. A haplotype defined by alleles at markers D19S49, D19S43, and D19S200 in chromosome 19 shows significant association (p < 0.003, odds ratio 2.82). Further, significant differences were observed in the distribution of the harm avoidance subscale among genotypes defined by D19S49 (p < 0.0001). These results provide evidence for the existence of a locus in chromosome 19 potentially involved in alcohol dependence susceptibility.
A more powerful method to evaluate p‐values in GENEHUNTER
Authors: Zhao Hongyu , Sheffield Leslie J. , Pakstis Andrew J. , Knauert Melissa P. , Kidd Kenneth K. 
Published: November 2013

AbstractThe determination of statistical significance in genetic linkage studies is complicated by many factors, such as missing individuals or uninformative markers, and the validity of theoretical results is often questionable. Although many simulation‐based methods have been proposed to determine empirically the statistical significance, they are either not generally applicable to complex pedigree structures, or not able to preserve the observed genetic information content at each locus in the pedigrees. We have developed and implemented a general and computationally efficient randomization procedure in GENEHUNTER that applies to arbitrary pedigree structure and preserves the observed information content at each locus. We applied this method to the Problem 1 data set of the Genetic Analysis Workshop 11. The performance of this new method was similar to the method implemented in GENEHUNTER‐PLUS, and both outperformed the conservative approach in GENEHUNTER.
Simulated data for a complex genetic trait (Problem 2 for GAW11): How the model was developed, and why
Authors: Greenberg David A. , Maccluer Jean W. , Spence M. Anne , Falk Catherine T. , Hodge Susan E. 
Published: November 2013

AbstractThis paper describes a simulated data set created as Problem 2 for GAW11. The generating model for Problem 2 involved two different genetic diseases, or “types,” in three separate populations. The two‐locus (2L) type results from the epistatic interaction of two genetic loci, and the three‐allele type, from a single locus with two disease‐causing alleles and one normal allele. Each type has two phenotypic forms: Mild and Severe. Both forms are subject to both genetic and environmental influences. The disease occurs in three different hypothetical populations, each with different disease allele frequencies and penetrances. In two populations there is also a fourth locus with an allele that is associated with the 2L type. Misdiagnosis can occur, but only after a family has already been ascertained through ≥ 2 “genetically” affected offspring. Finally, the three different populations are studied by four different hypothetical research groups. These groups each have their own ideas about how the disease is inherited and have therefore devised different ascertainment schemes based on those beliefs. Each research group collected 100‐family data sets, including data on 300 markers on six chromosomes and measurements on disease status and on the proposed two environmental factors. GAW participants were supplied with 25 random replicates of each data set.
Genetic model‐free linkage analysis using the maximum‐likelihood‐binomial method for categorical traits
Authors: Alcaïs Alexandre , Philippi Anne , Abel Laurent 
Published: November 2013

AbstractWithin the simulated data of the 11th Genetic Analysis Workshop, we searched for the genes controlling the disease. We analyzed 200 families from Studies 2 and 3 presenting both mild and severe forms of disease. Linkage analysis was performed using the recently developed genetic model‐free maximum‐likelihood‐binomial (MLB) method which overcomes the problem of multiple sibs by considering the sibship as a whole. The MLB allowed us to consider the disease as either a binary (affected/unaffected) or an ordered categorical (differentiating the two forms of disease and including effects of environmental factors) phenotype. In both studies, two regions provided evidence for linkage at a significance level below 10‐4. One is located on chromosome 3 (from D3G041 to D3G047), and the other on chromosome 5 (from D5G034 to D5G041). In Study 2, the most significant results were obtained by combining both forms of disease, suggesting that they are under the same genetic control, while in Study 3, the stronger results were obtained when considering severe subjects alone, suggesting that only the severe form is under the control of both locus B and C. The subsequent knowledge of the true model allowed a posterior interpretation of our results, in particular the difference in optimal coding schemes observed between Studies 2 and 3, and the failure to locate locus A.
Analysis of complex traits using neural networks
Authors: Bhat Ajita , Lucek Paul R. , Ott Jurg 
Published: November 2013

AbstractA recently developed approach that employs artificial neural networks (ANNs) was applied to the simulated data set to identify sets of marker loci involved in disease etiology. In this implementation, ANNs are trained to predict the disease state (output) from the given genetic marker data (input). A contribution value (CV) for each locus is calculated from the weights that represent the strength of the connections for the trained ANN; a higher CV indicates a higher probability of linkage. The highest CV values were chosen as the most likely candidate regions involved in the disease.
Multipoint linkage analysis using the weighted‐pairwise correlation statistic
Authors: Commenges Daniel , Beurton‐Aimar Marie 
Published: November 2013

AbstractThe weighted pairwise correlation (WPC) approach provides simple and flexible non‐parametric tests for genetic linkage which may be adapted to qualitative, quantitative or age‐dependent traits. Although this statistic has often been used with identity‐by‐state (IBS) information, there is much to gain by using multipoint identity‐by‐descent (IBD) information. The purpose of this paper is to use the unified multipoint approach of Kruglyak et al. [1996] with the WPC statistic. We used the simulated data of a complex disease proposed in GAW11 (problem 2) to validate this approach and to compare the multipoint WPC to the EBS‐WPC and to the multilocus approach using the conventional non‐parametric statistics Spairs and Sall. The results suggest that the multipoint WPC may be the most powerful approach.
Analysis of simulated data: Evidence for genetic and environmental effects
Authors: Crockford Gillian P. , Iles Mark M. , Durham L. Kathryn , Bishop D. Timothy 
Published: November 2013

AbstractWe approached the simulation as though it were an international study with similar but not identical information being collected from different populations. In keeping with this we analyzed one replicate from each population. Initially we examined the risk of disease in relatives of cases to determine whether the disease appeared to be “more genetic” in one population than in the others and we examined the evidence for environmental risk factors in each population. Non‐parametric linkage analysis and transmission/disequilibrium testing (TDT) were used to search for loci linked to the disease in each population. Using these methods we identified several candidate regions for a susceptibility gene which on examination of the answers are explicable in terms of the underlying model.
Hunting genetic diseases: Exploring a multistage approach to identifying disease loci
Authors: Garcia Melissa E. , Haines Jonathan L. 
Published: November 2013

AbstractGenomic screen data for a hypothetical disease was used in a two‐stage analysis to search for disease loci. We performed both trait‐model‐dependent and trait‐model‐free analyses to test their relative power. Results of our first‐stage screen in 200 families suggested 13 regions for further analysis. Second‐stage follow‐up in another 200 families confirmed a single region on chromosome 3 near marker D3G045 with a combined lod score across all 400 families of 6.24 and a sib‐pair maximum lod score (MLS) of 4.79. The MLS were highly correlated with both the autosomal dominant and autosomal recessive lod scores in all data sets, suggesting that both trait‐model‐dependent and trait‐model‐free methods can be useful for identifying candidate regions for complex disease loci. Reanalysis of the data using alternative sampling schemes suggested that sampling variation has a significant effect on locus detection.
A joint test of linkage and gene×environment interaction, with affected sib pairs
Authors: Gauderman W. James , Morrison John L. , Siegmund Kimberly D. , Thomas Duncan C. 
Published: November 2013

AbstractIn the presence of gene×environment (G×E) interaction, the expected proportion of alleles shared identical by descent at a linked marker locus by a pair of affected sibs depends on the exposure profile of the two sibs, i.e., whether both are exposed to E, only one is exposed, or neither are exposed. In this paper, we propose an extension of the commonly used mean test of linkage to test for differential identical‐by‐descent (IBD) sharing across sib‐exposure profiles. The method can be viewed as a test for linkage in the presence of G×E interaction, or as a test for G×E interaction in the presence of linkage. Applied to the simulated GAW11 data, our method successfully localized disease locus C and its interactive relationship with environmental factor E1. At the 5% significance level, use of our method led to increased power to detect linkage (56%) to this disease locus compared to use of the standard mean test (32%); at the 0.001 significance level, the corresponding power estimates were 20% and 4%, respectively. For a gene that interacts with an environmental factor, we conclude that use of the environmental factor in linkage analysis can improve detection rates while also providing information about underlying mechanisms.
Impact of family structure on the power of linkage tests using sib‐pair methods
Authors: Goddard Katrina A.B. , Goode Ellen L. , Rozek Laura S. , Jarvik Gail P. 
Published: November 2013

AbstractThis analysis sought to determine the impact of specific ascertainment criteria based upon nuclear family affectation structures. Specifically, we evaluated the predicted and observed proportion of alleles shared identical by descent conditional on the number of affected and unaffected siblings in a pedigree, and compared sib‐pair method linkage results under two ascertainment schemes, random vs. selected ascertainment, for this simulated complex genetic disease. These results suggest that samples differing in the composition of affected and unaffected siblings in the family will differ in their power to detect linkage. An effect of sampling scheme on power to map using affected‐sib‐pair methods should be considered when a reported linkage is not found in another study population.
Validation of linkage by sampling based on environmental exposures
Authors: Greenwood Celia M.T. , Brewer Carl G. , Morgan Kenneth 
Published: November 2013

AbstractAfter detecting linkage in one sample, most researchers will attempt to validate this finding in another sample. Three strategies for validating a primary linkage were compared, with a focus on methods that might be appropriate in the presence of gene×environment interaction. First, a validation sample was collected and analyzed using the same ascertainment procedure and methods as the primary sample. Second, a sample of families with particular exposure patterns were ascertained subsequent to a significant test for heterogeneity due to the exposure in the primary sample. A third strategy ascertained by exposure status when exposure‐defined subgroup tests were significant in the primary sample. The second strategy reduced the number of false positive linkage signals identified through exposure subgroup identification (i.e., the third strategy), but in this GAW11 data that contained no qualitative gene×environment interactions, it had poor sensitivity. Power to detect heterogeneity depends on the differences in risk between exposed and unexposed.
The Study of Gel Formation and Flocculation in Aqueous Clay Dispersions by Optical and Rheological Methods
Authors: Neumann Barbara S. , Sansom K. G. 
Published: November 2013

AbstractOptical and Theological methods have been used to study the gelling and flocculation of aqueous dispersions of a synthetic hectorite‐like clay, Laponite CP, on the addition of electrolytes or water miscible organic solvents. There is a positive correlation between the yield value and turbidity when the dispersions are flocculated with electrolyte. Addition of polar solvent, however, shows no such correlation, only a sudden change from very clear to very cloudy dispersion, while the yield value increases gradually until gross flocculation takes place. It is suggested that two different flocculation mechanisms are being observed.
Quartz Dissolution as Influenced by pH and the Presence of a Disturbed Surface Layer
Authors: Henderson J.H. , Syers J. K. , Jackson M. L. 
Published: November 2013

AbstractQuartz particles (10 to 2 microns in diameter, produced by grinding) released 45 ppm of SiO2 to a buffer solution of pH 7 during a 48 hr period. The grinding of quartz particles produced a disturbed surface layer with solubility properties intermediate between crystalline quartz (6 ppm SiO2) and amorphous silica (120 ppm SiO2). Removal of the disturbed layer by treatment with 1N HF lowered the SiO2 dissolution from 45 to 3 ppm. Use of 12N HF decreased the amount of SiO2 dissolved to 2 ppm, a result found to coincide with a preferential dissolution of the finer quartz particles in addition to the removal of the disturbed surface layer. The rate of dissolution of SiO2 from quartz particles, subsequent to treatment with 1N HF, increased with decrease in particle size, from 1 to 3 ppm for quartz particles 50 to 20 microns in diameter to 30 to 44 ppm for particles 2 to 0.2 microns in diameter, during each of three consecutive 14‐day extractions with pH 7 buffer solution. The amount of SiO2 dissolved from quartz in buffer solutions increased in the pH range of 4 to 10, from 0.6 ppm of SiO2 at pH 4 to 19 ppm at pH 10 during a 14‐day period of extraction from quartz particles, 10 to 2 microns in diameter. Quartz particles, subsequent to the removal of the disturbed surface layer, removed SiO2 from pH 4 and pH 8 buffer solutions prepared with more SiO2 in solution than would be released from quartz in the respective solution.
An Optical‐Transmission Study of the Interaction Between Montmorillonite and Humic Acids
Authors: Narkis N. , Rebhun M. , Lahav N. , Banin A. 
Published: November 2013

AbstractThe interaction between montmorillonite and kaolinite clay minerals and humic acid (HA) was studied in suspensions by absorbance measurements. Changes in absorbance as a result of the interaction were interpreted as an indication of changes in the size of clay tactoids. Na‐humate caused dissociation of montmorillonite tactoids in suspension. Drying‐wetting cycles increased the effect of Na‐humate and resulted in tactoids similar in their size to those of the Li‐saturated montmorillonite. Na‐humate had no effect on the absorbance of kaolinite suspensions.
N‐n‐Alkylpyridinium Derivatives of Mica‐Type Layer Silicates
Authors: Lagaly G. , Stange H. , Taramasso M. , Weiss Armin 
Published: November 2013

AbstractThis paper deals with the cation exchange of N‐n‐alkylpyridinium ions magnified image against inorganic ions in mica type layer silicates. The arrangements of these ions in the interlayer space is derived from basal spacing measurements.