Reproductive Risk Estimation Calculator for Balanced Translocation Carriers.

Balanced translocation carriers experience elevated reproductive risks, including pregnancy loss and children with anomalies due to generating chromosomally unbalanced gametes. While understanding the likelihood of producing unbalanced conceptuses is critical for individuals to make reproductive decisions, risk estimates are difficult to obtain as most balanced translocations are unique. To improve reproductive risk estimates, Drs.

Comparison of putative intermediate phenotypes in schizophrenia patients with and without obsessive-compulsive disorder: examining evidence for the schizo-obsessive subtype.

Obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) is estimated to occur in up to 30% of patients with schizophrenia. Whether this subgroup of patients is cognitively, affectively, or physiologically distinct remains unclear. 204 schizophrenia patients, 15 who also met criteria for a diagnosis of OCD, and 147 healthy controls were examined on several intermediate phenotypes.

The effects of perceptual encoding on the magnitude of object working memory impairment in schizophrenia.

Deficits in the visual working memory (WM) system have been consistently reported in schizophrenia patients, but the relative contribution of initial perceptual encoding to these deficits remains unsettled. We assessed the role of visual perceptual encoding on performance on an object WM task. Schizophrenia patients (N=37) and nonpsychiatric control subjects (N=33) were tested on an object WM task involving three delay periods: 200 ms, 3s, and 10s.

Principal components ancestry adjustment for Genetic Analysis Workshop 17 data.

Statistical tests on rare variant data may well have type I error rates that differ from their nominal levels. Here, we use the Genetic Analysis Workshop 17 data to estimate type I error rates and powers of three models for identifying rare variants associated with a phenotype: (1) by using the number of minor alleles, age, and smoking status as predictor variables; (2) by using the number of minor alleles, age, smoking status, and the identity of the population of the subject as predictor variables; and (3) by using the number of minor alleles, age, smoking status, and ancestry adjustment using 10 principal component scores. We studied both quantitative phenotype and a dichotomized phenotype.

Necessary and sufficient conditions for equality of sibling and parent-offspring risk of a disease endophenotype in case families.

A large number of linkage and association studies of complex diseases focus on analysis of a more common or more easily measured disease endophenotype. The motivation for this approach is that there is a pleiotropic locus common to both the disease and the endophenotype and that this locus is a major genetic determinant of the endophenotype. In this paper, we determine the conditions under which the risk of the endophenotype in siblings of affected probands with disease equals the risk of the endophenotype in the offspring (parents) of affected parents (offspring) with disease.

Patients' sex and emotional support as predictors of death and clinical deterioration in the waiting for a new heart study: results from the 1-year follow-up.

Context: Little is known about the role of patient's sex and emotional support in the prognosis of heart transplant candidates.

Objective: To examine patient's sex and emotional support as predictors of outcomes in the Waiting for a New Heart Study.

Design, Setting, And Participants: The Waiting for a New Heart Study is a prospective observational study of 318 patients (18% female) newly added to the waiting list for a heart transplant.

Clinical events in coronary heart disease patients with an ejection fraction of 40% or less: 3-year follow-up results.

Background And Research Objective: It is unclear whether lifestyle changes can delay the need for surgical procedures in coronary heart disease (CHD) patients with asymptomatic reduced left ventricular ejection fraction (LVEF). The aim of this pilot study was to examine whether lifestyle changes can delay the need for surgical procedures in this population.

Subjects And Methods: We compared 3-year clinical events in 27 CHD patients eligible to receive revascularization (by insurance standards), but underwent lifestyle changes (low-fat diet, exercise, stress management) instead (intervention group [IG], LVEF < or =40%), with those of a historically matched (age, gender, LVEF, and stenosis of the 3 major coronary arteries) control group receiving usual care (UCG; n = 13) who received revascularization at study entry.

Parent-child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder.

The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent-child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother-child (MC) and father-child (FC) dyads.

Little genetic differentiation as assessed by uniparental markers in the presence of substantial language variation in peoples of the Cross River region of Nigeria.

Background: The Cross River region in Nigeria is an extremely diverse area linguistically with over 60 distinct languages still spoken today. It is also a region of great historical importance, being a) adjacent to the likely homeland from which Bantu-speaking people migrated across most of sub-Saharan Africa 3000-5000 years ago and b) the location of Calabar, one of the largest centres during the Atlantic slave trade. Over 1000 DNA samples from 24 clans representing speakers of the six most prominent languages in the region were collected and typed for Y-chromosome (SNPs and microsatellites) and mtDNA markers (Hypervariable Segment 1) in order to examine whether there has been substantial gene flow between groups speaking different languages in the region.

The Genetic Basis of Thought Disorder and Language and Communication Disturbances in Schizophrenia.

Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself.

The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs.

A linkage study of a qualitative disease endophenotype in a sample of sib pairs, consisting of one disease affected proband and one sibling is considered. The linkage statistic compares marker allele sharing with the proband in siblings with an abnormal endophenotype to siblings with the normal endophenotype. Expressions for the distribution of this linkage statistic, in terms of the recombination fraction are derived and (1) the genetic parameter values (allele frequency and endophenotype and disease penetrance) and (2) the abnormal endophenotype rates in the population and in classes of relatives of disease affected probands.

Family-based analysis of a myocardial infarction endophenotype: comparison of sampling designs.

The power of linkage analysis of a quantitative disease endophenotype was compared for the following family selection designs: 1) Random samples: randomly chosen nuclear families, 2) "coronary artery calcification (CAC)" samples: selection of each nuclear family through a proband with abnormally high levels of the simulated quantitative endophenotype, CAC, and (3) "MI" samples: selection of each nuclear family through a disease affected proband, in this case a proband who had been simulated to have a myocardial infarction (MI) event.We assessed the power to detect linkage to five loci (two pairs of epistatic loci and one locus with an over-dominant allele) that were modeled as determinants of the simulated CAC levels. We did this using a Haseman-Elston regression-based linkage analysis of the adjusted CAC levels that considered each locus separately and then used a multiple regression extension of the Haseman-Elston method in which we considered the allele sharing at two true epistatic loci simultaneously and their interaction as possible factors related to the squared sibpair differences in adjusted CAC.

Growth mixture modeling as an exploratory analysis tool in longitudinal quantitative trait loci analysis.

We examined the properties of growth mixture modeling in finding longitudinal quantitative trait loci in a genome-wide association study. Two software packages are commonly used in these analyses: Mplus and the SAS TRAJ procedure. We analyzed the 200 replicates of the simulated data with these programs using three tests: the likelihood-ratio test statistic, a direct test of genetic model coefficients, and the chi-square test classifying subjects based on the trajectory model's posterior Bayesian probability.

Tailoring the definition of the clinical schizophrenia phenotype in linkage studies.

The delineation of schizophrenia-related symptomatology is critical to informative clinical phenotyping in linkage studies. A minority of first-degree relatives of schizophrenia and schizoaffective probands (RelSZSA) qualifies for a clinical diagnosis in the schizophrenia spectrum. Schizotypal personality disorder (SPD) is a key component of this spectrum, largely because of its relatively specific familial aggregation in relatives.

Microduplications of 16p11.2 are associated with schizophrenia.

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.

Social isolation and depression predict 12-month outcomes in the "waiting for a new heart study".

Background: Identification of modifiable psychosocial characteristics related to survival of heart transplant (HTx) candidates is needed to prevent clinical deterioration and improve prognosis.

Methods: A multi-site, prospective study was conducted with 318 HTx candidates (18% female, 82% male; 53 +/- 11 years of age) newly listed at 17 hospitals in Germany and Austria. Baseline demographic and psychosocial characteristics were assessed by questionnaires.

Schizophrenia patients show deficits in shifts of attention to different levels of global-local stimuli: evidence for magnocellular dysfunction.

Abnormalities of attention and visual perception are well documented in schizophrenia. The global-local task is a measure of attention and perceptual organization that utilizes visual stimuli comprised of large letters (global level) made up of smaller letters (local level). Subjects identify target letters appearing at either the global or local level of the stimulus.

Reinforcement ambiguity and novelty do not account for transitive inference deficits in schizophrenia.

The capacity for transitive inference (TI), a form of relational memory organization, is impaired in schizophrenia patients. In order to disambiguate deficits in TI from the effects of ambiguous reinforcement history and novelty, 28 schizophrenia and 20 nonpsychiatric control subjects were tested on newly developed TI and non-TI tasks that were matched on these 2 variables. Schizophrenia patients performed significantly worse than controls on the TI task but were able to make equivalently difficult nontransitive judgments as well as controls.

Sex-Specific Genetic Data Support One of Two Alternative Versions of the Foundation of the Ruling Dynasty of the Nso' in Cameroon.

Sex-specific genetic data favor a specific variant of the oral history of the kingdom of Nso' (a Grassfields city-state in Cameroon) in which the royal family traces its descent from a founding ancestress who married into an autochthonous hunter-gatherer group. The distributions of Y chromosome and mitochondrial DNA variation in the Nso' in general and in the ruling dynasty in particular are consistent with specific Nso' marriage practices, suggesting strict conservation of the royal social class along agnatic lines. This study demonstrates the efficacy of using genetics to augment other sources of information (e.

Does performance on the standard antisaccade task meet the co-familiality criterion for an endophenotype?

The "co-familiality" criterion for an endophenotype has two requirements: (1) clinically unaffected relatives as a group should show both a shift in mean performance and an increase in variance compared with controls; (2) performance scores should be heritable. Performance on the antisaccade task is one of several candidate endophenotypes for schizophrenia. In this paper we examine whether the various measures of performance on the standard version of the antisaccade task meet the co-familiality criterion for an endophenotype.

The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa.

Background: The drug-metabolizing enzyme flavin-containing monooxygenase 2 (FMO2) is the predominant FMO isoform present in the lung of most mammals, including non-human primates. All Europeans and Asians tested have been shown to be homozygous for a non-functional variant, FMO2*2A, which contains a premature stop codon due to a single-nucleotide change in exon 9 (g.23238C>T).

Mixture modeling of microarray gene expression data.

About 28% of genes appear to have an expression pattern that follows a mixture distribution. We use first- and second-order partial correlation coefficients to identify trios and quartets of non-sex-linked genes that are highly associated and that are also mixtures. We identified 18 trio and 35 quartet mixtures and evaluated their mixture distribution concordance.

Incorporation of genetic model parameters for cost-effective designs of genetic association studies using DNA pooling.

Background: Studies of association methods using DNA pooling of single nucleotide polymorphisms (SNPs) have focused primarily on the effects of "machine-error", number of replicates, and the size of the pool. We use the non-centrality parameter (NCP) for the analysis of variance test to compute the approximate power for genetic association tests with DNA pooling data on cases and controls. We incorporate genetic model parameters into the computation of the NCP.

Increasing power for tests of genetic association in the presence of phenotype and/or genotype error by use of double-sampling.

Phenotype and/or genotype misclassification can: significantly increase type II error probabilities for genetic case/control association, causing decrease in statistical power; and produce inaccurate estimates of population frequency parameters. We present a method, the likelihood ratio test allowing for errors (LRTae) that incorporates double-sample information for phenotypes and/or genotypes on a sub-sample of cases/controls. Population frequency parameters and misclassification probabilities are determined using a double-sample procedure as implemented in the Expectation-Maximization (EM) method.