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PubMed2004

A fast algorithm for functional mapping of complex traits.

By integrating the underlying developmental mechanisms for the phenotypic formation of traits into a mapping framework, functional mapping has emerged as an important statistical approach for mapping complex traits. In this note, we explore the feasibility of using the simplex algorithm as an alternative to solve the mixture-based likelihood for functional mapping of complex traits. The results from the simplex algorithm are consistent with those from the traditional EM algorithm, but the simplex algorithm has considerably reduced computational times. Moreover, because of its nonderivative nature and easy implementation with current software, the simplex algorithm enjoys an advantage over the EM algorithm in the dynamic modeling and analysis of complex traits.

Algorithms↗
PubMed1996

Influence of alpha-thalassemia trait on spleen function in sickle cell anemia patients with high HbF.

Spleen function was studied in a group of 20 Kuwaiti SS patients (aged 2-12 years), using 99mTc-labeled tin colloid scintigraphy. They were screened for the alpha-thalassemia determinants which are prevalent in the Arabian Peninsula [-alpha (3.7 kb) deletion, alpha2-globin gene polyadenylation signal (AATAAA => AATAAG) mutation, and 5' IVS-I splice junction pentanucleotide (GAGGTGAGG => GAGG) deletion] with a combination of polymerase chain reaction and allele-specific oligonucleotide (ASO) hybridization techniques. The patients were divided into three groups depending on the result of their colloid uptake. Group I consisted of 7 patients (35.0%) with normally visualized spleens, Group II consisted of 5 (25.0%) with partial visualization, and in Group III there were 8 (40.0%) in whom the spleen was not visualized at all. The significant distinguishing features among those in Groups I and III were mean corpuscular volumes (MCVs) of 74.1 +/- 5.1 and 90.1 +/- 6.6 fl (P<0.0001) and mean corpuscular hemoglobins (MCHs) of 22.4 +/- 2.7 and 27.5 +/- 4.0 pg (P<0.05), respectively. The overall frequency of alpha-thalassemia determinants in the study was 35.0%; however, the frequencies in Groups I, II, and III were 57.1, 30.0, and 18.8%, respectively. alpha-Thalassemia trait, therefore, appears to be associated with normal splenic function in these patients.

Age Factors↗
PubMed1979

Speech clinicians' attribution of personality traits as a function of stuttering severity.

Thirty-six speech-language pathologists participated in a study to evaluate clinicians' preconceptions of persons who stutter. Each rated a designated construct (the normally fluent individual, the mild stutterer, the moderate stutterer, the severe stutterer) using a personality trait scale. Results indicated that clinicians stereotypically assign negative personality traits to all levels of stuttering severity relative to normal. Their ratings further demonstrated that stutterers are generally considered to be a homogenous group. Differentiation amongst stutterers was made only between the polar ends of the stuttering severity continuum (that is, mild vs. severe). Clinicians' sterotypical trait assignment was not related to their professional experience. Results are discussed with reference to their clinical implications.

Humans↗
PubMed2006

Predicting domain-specific insight of schizophrenia patients from symptomatology, multiple neurocognitive functions, and personality related traits.

This study examines the contribution of various neurocognitive functions, clinical characteristics, and personality traits to the prediction of three insight dimensions. Clinically stable schizophrenia patients (n=107) residing in the community were evaluated using the Positive and Negative Syndrome Scale, the Scale for the Assessment of Unawareness of Mental Disorder, and a comprehensive battery of instruments to measure personality related variables and neurocognitive functioning. Step-wise multivariate regression analysis indicates significant association of variability in insight dimensions with neurocognitive functioning (20-41%), personality related traits (8-18% temperament factors, 4-7% self-constructs, 10-14% coping styles), severity of symptoms (about 7%), illness duration (6%), and education (about 5%). Poor insight was attributed to impairment in visual and movement skills, sustained attention, executive functions, intensity of autistic preoccupations and positive symptoms, as well as increased novelty seeking behavior, task and emotion oriented coping styles, better self-esteem, self-efficacy, and higher education. Better awareness was related to better performance of neurocognitive tasks, reward dependence behavior, avoidant coping style, and longer illness duration. Aside from common indicators for the various insight dimensions, we defined specific indicators for each insight dimension. Thus, insight dimensions in schizophrenia patients residing in the community were attributed to neurocognitive and personality related factors rather than to psychopathological symptoms. The findings enable better understanding of the multifactorial nature of insight and highlight targets for more effective intervention and rehabilitation.

Adaptation, Psychological↗
PubMed2005

Auditory P3 indexes personality traits and cognitive function in healthy men and women.

The relationship of the auditory P3 event-related potential to major personality dimensions and neuropsychological performance was examined in psychiatrically healthy men and women (28 male, 15 female) recruited from the community. An auditory oddball paradigm was used to collect P3 amplitude and latency data. Personality traits were measured with the NEO Five-Factor Inventory. Several Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtests, the Digit Symbol Test, and the Trail Making Test comprised the neuropsychological tests. A multivariate statistical procedure (Partial Least Squares) was used to quantify the relationships between P3 variables and personality and neuropsychological performance variables. P3 amplitude was negatively related to Neuroticism and positively related to Extraversion, Openness, Agreeableness and Conscientiousness. Better neuropsychological performance was associated with greater P3 amplitude and earlier latency. Thus, greater P3 amplitude was associated with less deviant personality scores and better neuropsychological performance in healthy subjects. Earlier P3 latency was also associated with better neuropsychological performance. The physiological significance of these relationships is not yet clear, but these results suggest that neural assemblies indexed by P3 may subserve both elemental cognition and healthy personality function.

Adolescent↗
PubMed2004

Serotonin function, personality-trait variations, and childhood abuse in women with bulimia-spectrum eating disorders.

BACKGROUND: Across populations, findings associate impulsivity, behavioral disinhibition, or hostility with reduced central serotonin (5-hydroxytryptamine: 5-HT) activity and increased likelihood of childhood abuse. Inconsistently, findings associate compulsivity, behavioral inhibition, or anxiousness with elevated 5-HT neurotransmission. We explored relationships among measures of 5-HT system functioning, behavioral inhibition/disinhibition, and childhood abuse in women with bulimia-spectrum eating syndromes. METHOD: In 73 bulimic (body mass index [kg/m2] under 30, binge eating at least once weekly) and 50 normal-eater control women, we obtained indices of platelet paroxetine binding and 5-HT agonist (m-CPP)-stimulated neuroendocrine responses. Cluster analysis was used to classify the bulimic women according to 5-HT "profiles." Resulting groups were then compared on symptom and trait measures. RESULTS: Measures of paroxetine-binding density (Bmax) and affinity (Kd) contributed significantly (p < .001 and p < .02, respectively) to a classification of bulimic women into groups with "low density/high affinity" (N = 52) or "high density/low affinity" (N = 21) binding. The 5-HT based classification did not predict eating-symptom severity. However, the "high density" pattern was associated with increased perfectionism and compulsivity, reduced risk of childhood sexual abuse, and (to some extent) reduced probability of borderline personality disorder. DISCUSSION: In women with bulimic syndromes, serotonergic factors, personality-trait variations, and developmental typologies converge in principled fashion. Our findings corroborate (with neurobiological evidence) the concept of underregulated and overregulated subtypes within the bulimic population.

Adolescent↗
PubMed2005

Limited effect of intense genetic selection for broiler traits on ovarian function and follicular sensitivity in broiler breeders at the onset of lay.

Female chicks from 6 pure lines of broiler breeders were obtained from international broiler breeder companies. The lines were from three female and two male lines and a relaxed selection line derived from one of the male lines (M2) and maintained without selection for 25 years (generations). Replicate groups from each line were reared in floor pens and fed ad libitum. An additional group of the M2 male line was feed restricted and housed in similar pens. Twenty birds from each group were photostimulated after housing them in individual cages at 14 weeks of age. Ovarian follicular dynamics and follicular sensitivity were determined after the onset of lay. Female lines had a greater proportion of atretic follicles and more groups of multiple follicles than male lines. Body weights, fatness and age at puberty were similar in male and female lines. The relaxed selection line had more abdominal fat than any of the selected lines and the ovary contained a similar number of normal yellow follicles as the selected male line. Feed restriction decreased body weight, the numbers of yellow follicles, multiple yellow follicles and the proportion of atretic yellow follicles, and increased the age at onset of lay. The response of ovarian follicles of three different sizes to exogenous gonadotrophin stimulation with PMSG was similar in small yellow follicles, 5 to 6 and 2 to 3 mm white follicles in a female line, a male line and its relaxed line fed ad libitum. The results suggest that the original lines from which modern male-line broiler stocks are derived had a relatively large number of yellow follicles and a high propensity for multiple ovulation at the onset of lay. Separate selection for different traits in male and female lines has not had a dramatic effect on ovarian function or sensitivity to gonadotrophin stimulation.

Aging↗
PubMed1996

Tumour necrosis factor soluble receptors I and II and interleukin-1 receptor antagonist in acute pyelonephritis in relation to bacterial virulence-associated traits and renal function.

Urinary tract infections activate both mucosal and systemic inflammatory responses reflected by elevation of cytokine concentrations in serum and urine. We determined urine and serum concentrations of tumour necrosis factor soluble receptors I and II (sTNFR I and sTNFR II) and interleukin-1 receptor antagonist (IL-1ra) in 41 women with acute pyelonephritis caused by Escherichia coli, 2 weeks after the infection, during a subsequent episode of cystitis or asymptomatic bacteriuria and also later when the same patients were free from bacteriuria. Concentrations of sTNFR I, sTNFR II and IL-1ra were related to the expression of five virulence markers of E. coli, glomerular filtration rate (GFR) and to the concentration of C-reactive protein (CRP) in serum. Patients with acute pyelonephritis had elevated serum concentrations of sTNFR I and sTNFR II compared to healthy women (P < 0.001 for both comparisons). The concentrations of sTNFR I and sTNFR II in urine were significantly higher in patients with acute pyelonephritis compared to controls (P < 0.001 in both cases). The concentration of sTNFR II in urine was higher in patients infected by E. coli producing haemolysin (P = 0.05) and in patients infected by E. coli expressing hydrophobic properties (P = 0.05) compared to patients infected by strains without these virulence traits. Patients who had high concentrations of sTNFR II in serum during acute pyelonephritis had lower GFR at follow-up (r = -0.48, P = 0.05). Patients who responded with a marked increase in CRP had higher sTNFR I and sTNFR II in urine (r = 0.58, P < 0.01 and r = 0.48, P < 0.01, respectively). The concentrations of sTNFR I and sTNFR II in serum and urine decreased during follow-up and were lower 2 weeks after the infection when all patients were free from bacteriuria. IL-1ra in serum was elevated during pyelonephritis (P < 0.001) while that in urine was significantly lower compared to controls (P < 0.001). It is concluded that the increased concentrations of TNF receptors may block the cytotoxic and inflammatory actions and reduce the sensibility of renal cells to TNF alpha-mediated effects.

Acute Disease↗
PubMed2000

Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs.

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P = 0.03), including the subscale of shyness (P = 0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits.

Adolescent↗
PubMed1992

Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits.

To gain insight into the variable expression of lung disease in alpha 1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack-years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals.

Family↗
PubMedDate not supplied

Relationships between psychological mindedness and personality traits and ego functioning: validity studies.

Two studies further investigated the psychometric properties of the self-report Psychological Mindedness Scale (PMS), which has been shown to have good internal consistency and evidence of predictive and divergent validity. Its construct validity was investigated by assessing (1) whether total scores on the PMS of a group of medical students attending a personnel clinic in a psychiatric outpatient setting would be related in theoretically expected ways to their scores on a personality test; and (2) whether total scores on the PMS of a group of regular clinic patients would have the expected theoretical relationships to scores on a measure of ego functions. The findings of both studies provided support for the construct validity of the PMS.

Adaptation, Psychological↗
PubMed1983

Environmental adaptation of proteins: strategies for the conservation of critical functional and structural traits.

Comparative studies of lactate dehydrogenases (LDHs) and skeletal muscle actins from vertebrates adapted to widely different temperatures and hydrostatic pressures reveal major conservative trends in protein evolution and adaptation. For enzymes, ligand binding, as estimated by apparent Michaelis constant (Km) values, is strongly conserved at physiological temperatures, pressures, intracellular pH values and osmotic compositions of different organisms. The catalytic rate constants (kcat values) of enzyme homologues are highest for enzymes of low-body-temperature organisms, a trend that can be interpreted in terms of temperature compensation of metabolism. For skeletal muscle actins, the enthalpy and entropy changes accompanying the assembly of filamentous (F) actin from globular (G) actin are highest in high-body-temperature species and especially low in polar and deep-sea fishes. The thermal stability of G-actin is positively correlated with adaptation temperature, except in the case of actins of deep-sea fishes, which are also highly heat stable. Hydrophobic interactions between actin subunits may be of reduced importance in low-body-temperature animals and, especially, in deep-sea fishes. The differences in enthalpy and entropy changes during the G-to-F transformation favor a close conservation of the equilibrium constant for actin assembly under physiological conditions of temperature and pressure for different species. These adaptive patterns in enzymes and actin are likely to reflect changes in protein primary structure. The appropriate values for protein traits such as ligand binding abilities and catalytic rates are also shown to be established by the composition of the low molecular weight constituents of the cytosol. For example, the use of a combination of urea and methylamine solutes for osmoregulation by marine elasmobranchs is shown to be a mechanism which permits the conservation of key protein traits at high osmolarities. The methylamine solutes such as trimethylamine-N-oxide have effects on proteins opposite to those of urea, and at the approximately 2:1 concentration ratio of urea to methylamines, these counteracting effects are virtually complete. Regulation of hydrogen ion activity (pH) also is shown to play a major role in the conservation of critical protein traits. The importance of temperature-dependent pH in ectotherms is discussed in terms of stabilizing binding abilities and maintaining correct regulatory and structural sensitivities of proteins. The buffering capacity of tissues reflects the potential of the tissue for generating acidic end-products during anaerobic metabolism. Skeletal muscle, especially white locomotory muscle of fishes, is highly buffered relative to red locomotory muscle and heart muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed2000

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT).

Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol O-methyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT x 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR x D4DR (F = 6.18, P = 0.03) and COMT x 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry (2000) 5, 96-100.

Adolescent↗
PubMedDate not supplied

Associations between psychological traits and endothelial function in postmenopausal women.

OBJECTIVE: The objective of this study was to determine whether psychosocial risk factors for cardiovascular disease (CVD) are associated with impairments in endothelial function and to determine whether use of hormone replacement therapy (HRT) can moderate observed associations among women without prior CVD. METHODS: Flow-mediated dilation was assessed by brachial ultrasound after reactive hyperemia in 193 postmenopausal women enrolled in the prospective Healthy Women Study. Measures of psychosocial characteristics had been completed at study entry, when the women were premenopausal (mean = 13.6 years earlier), and at a separate postmenopausal follow-up exam near the time of the ultrasound (mean = 1.5 years earlier). RESULTS: Factor analyses of the psychosocial characteristics yielded two factors: Type A/anger and anxiety/depression. Anxiety/depression scores at the study entry and follow-up exams and Type A/anger scores at the study entry exam were associated with less vasodilation (p values < 0.05). Type A/anger scores at the follow-up exam were associated with less vasodilation among women not using HRT (p <.05). CONCLUSIONS: Psychosocial risk factors for CVD are associated with impaired brachial artery dilation among postmenopausal women. HRT use may mask some associations between psychosocial risk factors and endothelial dysfunction among postmenopausal women.

Aged↗
PubMedDate not supplied

Relationship between cannabis use, schizotypal traits, and cognitive function in healthy subjects.

This research examined the relationship between cannabis use and schizotypal features. A sample of cannabis users (n = 20) was compared with a matched control group (n = 20). All participants were male students of the University of Hamburg. Subjects completed the Perceptual Aberration Scale and the Schizotypal Personality Questionnaire. A Negative Priming procedure and the Trail Making Test were carried out. A urine sample was obtained from each subject. Cannabis users exceeded controls in schizotypy scores and showed impaired neuropsychological parameters. Only within the cannabis group schizotypy scores correlated with neuropsychological parameters. Furthermore, cannabis users reported more often high-risk factors than controls. These findings indicate that among cannabis users there is an increased number of subjects with schizotypal features; schizotypal subjects seem to be more likely to use cannabis than the general population. Therefore, cannabis use may be a vulnerability indicator for schizophrenia.

Adult↗
PubMed1994

Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial-virulence-associated traits and renal function.

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Acute Disease↗
PubMedDate not supplied

[Pharmacological analysis of the ontogenetic traits of the functional receptor activity of glial and neuronal GABA uptake and GABA-T activity in the rat hippocampus].

Studies have been made on the effect of GABA mimetics on epileptogenic focus in the hippocamp of growing rats. By the pattern of inhibition of this focus by these drugs, it is possible to evaluate the degree of functional maturation of the activity of GABA receptors, glial and neuronal uptake of GABA, and the activity of GABA-T. Higher sensitivity of GABA receptors in younger animals was found together with a higher functional role of glial uptake in GABA utilization. Functional activity of GABA-T and neuronal uptake of the mediator are of lower physiological significance in younger animals as compared to those in adults.

4-Aminobutyrate Transaminase↗