Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families.

Objectives: Recent work shows promising associations between schizophrenia and polymorphisms in neuregulin-1 (NRG1) and a large literature also finds strong familial relationships between schizophrenia and cognitive deficits. Given the role of NRG1 in glutamate regulation and glutamate's effect on cognition, we hypothesized that cognitive deficits may be related to variation within NRG1, providing a possible mechanism to increase risk for schizophrenia.

Methods: This study examined the associations between NRG1, cognition, and schizophrenia using a multigenerational multiplex family sample (total N=419, 40 families), including 58 affected participants (schizophrenia or schizoaffective disorder-depressed type) and their 361 unaffected relatives.

Systems genetics of the nuclear factor-κB signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging.

A theory of aging holds that senescence is caused by a dysregulated nuclear factor kappa B (NF-κB) signal transduction network (STN). We adopted a systems genetics approach in our study of the NF-κB STN. Ingenuity Pathways Analysis (IPA) was used to identify gene/gene product interactions between NF-κB and the genes in our transcriptional profiling array.

Introduction to genetic analysis workshop 17 summaries.

Genetic Analysis Workshop 17 (GAW17) was held on October 13-16, 2010, in Boston, Massachusetts. The focus of GAW17 was on methods and challenges of the analysis of next-generation sequence data using a mini-exome data set. Two different study designs were simulated, unrelated individuals and large families, each with the same sample size.

High dimensional endophenotype ranking in the search for major depression risk genes.

Background: Despite overwhelming evidence that major depression is highly heritable, recent studies have localized only a single depression-related locus reaching genome-wide significance and have yet to identify a causal gene. Focusing on family-based studies of quantitative intermediate phenotypes or endophenotypes, in tandem with studies of unrelated individuals using categorical diagnoses, should improve the likelihood of identifying major depression genes. However, there is currently no empirically derived statistically rigorous method for selecting optimal endophentypes for mental illnesses.

Heritability of cognitive functions in families of successful cognitive aging probands from the Central Valley of Costa Rica.

We sought to identify cognitive phenotypes for family/genetic studies of successful cognitive aging (SCA; maintaining intact cognitive functioning while living to late old age). We administered a battery of neuropsychological tests to nondemented nonagenarians (n = 65; mean age = 93.4 ± 3.

Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder.

Background: Bipolar disorder (BPD) has been associated with variations in personality dimensions, but the nature of this relationship has been unclear. In this study, the heritabilities of BPD and the Big Five personality factors and the genetic correlations between BPD and personality factors are reported.

Methods: The participants in this study were 1073 individuals from 172 families of Mexican or Central American ancestry.

Influence of cholesterol and β-sitosterol on the structure of EYPC bilayers.

The influence of cholesterol and β-sitosterol on egg yolk phosphatidylcholine (EYPC) bilayers is compared. Different interactions of these sterols with EYPC bilayers were observed using X-ray diffraction. Cholesterol was miscible with EYPC in the studied concentration range (0-50 mol%), but crystallization of β-sitosterol in EYPC bilayers was observed at X ≥ 41 mol% as detected by X-ray diffraction.

Copy number variation accuracy in genome-wide association studies.

Background/aim: Copy number variations (CNVs) are a major source of alterations among individuals and are a potential risk factor in many diseases. Numerous diseases have been linked to deletions and duplications of these chromosomal segments. Data from genome-wide association studies and other microarrays may be used to identify CNVs by several different computer programs, but the reliability of the results has been questioned.

Network structure of polyfluorene sheets as a function of alkyl side chain length.

The formation of self-organized structures in poly(9,9-di-n-alkylfluorene)s ∼1 vol % methylcyclohexane (MCH) and deuterated MCH (MCH-d(14)) solutions was studied at room temperature using neutron and x-ray scattering (with the overall q range of 0.00058-4.29 Å(-1)) and optical spectroscopy.

Common genetic influences on depression, alcohol, and substance use disorders in Mexican-American families.

Multiple genetic and environmental factors influence the risk for both major depression and alcohol/substance use disorders. In addition, there is evidence that these illnesses share genetic factors. Although, the heritability of these illnesses is well established, relatively few studies have focused on ethnic minority populations.

Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes.

Although disrupted in schizophrenia 1 (DISC1) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted transcriptional profiling and genome-wide association analysis in 1232 pedigreed Mexican-American individuals for whom we have neuroanatomic images, neurocognitive assessments and neuropsychiatric diagnoses. SOLAR was used to determine heritability, identify gene expression patterns and perform association analyses on 188 quantitative brain-related phenotypes.

Molecular clusters in aqueous solutions of pyridine and its methyl derivatives.

Small-angle neutron scattering proved that molecules in aqueous solutions of pyridine, 2-methylpyridine and 2,6-dimethylpyridine form clusters. The clusters are dynamic aggregates consisting of hydrogen-bonded water-amine complexes. Strengthening of the hydrogen bonds between water and amine molecules due to the methyl groups in the ortho position in the pyridine ring makes the structures more stable, as was evidenced by relatively long times of the structural relaxation.

Nonreplication of an association of SGIP1 SNPs with alcohol dependence and resting theta EEG power.

A recent study in a sample of Plains Indians showed association between eight single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and resting θ electroencephalogram (EEG) power. This association appeared to generalize to alcohol use disorders, for which EEG power is a potential endophenotype. We analyzed a large, diverse sample for replication of the association of these implicated SGIP1 SNPs (genotyped on the Illumina 1M platform) with alcohol dependence (N=3988) and θ EEG power (N=1066).

Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.

Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association.

A quantitative trait locus on chromosome 5p influences d-dimer levels in the san antonio family heart study.

Background. D-dimer is associated with increasing severity of atherosclerosis and with increased risk of a cardiovascular disease (CVD). Methods and Results.

Blood pressure and cerebral white matter share common genetic factors in Mexican Americans.

Elevated arterial pulse pressure and blood pressure (BP) can lead to atrophy of cerebral white matter (WM), potentially attributable to shared genetic factors. We calculated the magnitude of shared genetic variance between BP and fractional anisotropy of water diffusion, a sensitive measurement of WM integrity in a well-characterized population of Mexican Americans. The patterns of whole-brain and regional genetic overlap between BP and fractional anisotropy were interpreted in the context the pulse-wave encephalopathy theory.

Genetic influences on serum bilirubin in American Indians: The Strong Heart Family Study.

Objective: To identify genetic variation influencing serum bilirubin levels in American Indians, we performed genome-wide screening and association analyses in the Strong Heart Family Study. Bilirubin is an endogenous antioxidant that has demonstrated an inverse relationship with cardiovascular disease. Genetic variation within the promoter region of uridine diphosphate glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with elevated serum bilirubin levels in European populations.

Structure and "surfactochromic" properties of conjugated polyelectrolyte (CPE): surfactant complexes between a cationic polythiophene and SDS in water.

We report on the phase transitions, solution structure, and consequent effect on the photophysical properties of poly[3-(6-trimethylammoniumhexyl)thiophene] bromide (P3TMAHT) in aqueous sodium dodecylsulfate (SDS). Polythiophene was mixed with SDS or deuterated SDS to form P3TMAHT(SDS)(x) complex (x = the molar ratio of surfactant over monomer units) in D(2)O and studied by small-angle neutron and X-ray scattering (SANS/SAXS) and optical spectroscopy. At room temperature, P3TMAHT forms charged aggregates with interparticle order.

Predicting sensation seeking from dopamine genes. A candidate-system approach.

Sensation seeking is a heritable personality trait that has been reliably linked to behavioral disorders. The dopamine system has been hypothesized to contribute to variations in sensation seeking between different individuals, and both experimental and observational studies in humans and nonhuman animals provide evidence for the involvement of the dopamine system in sensation-seeking behavior. In this study, we took a candidate-system approach to genetic association analysis of sensation-seeking behavior.

Whole brain and regional hyperintense white matter volume and blood pressure: overlap of genetic loci produced by bivariate, whole-genome linkage analyses.

Background And Purpose: The volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity with a demonstrated high heritability. Pathophysiology studies have shown that the regional, ependymal, and subcortical HWM lesions are associated with elevated arterial pulse pressure and arterial blood pressure (BP), respectively. We performed bivariate, whole-genome linkage analyses for HWM volumes and BP measurements to identify chromosomal regions that contribute jointly to both traits in a population of healthy Mexican Americans.

Transcriptomic epidemiology of smoking: the effect of smoking on gene expression in lymphocytes.

Background: This investigation offers insights into system-wide pathological processes induced in response to cigarette smoke exposure by determining its influences at the gene expression level.

Methods: We obtained genome-wide quantitative transcriptional profiles from 1,240 individuals from the San Antonio Family Heart Study, including 297 current smokers. Using lymphocyte samples, we identified 20,413 transcripts with significantly detectable expression levels, including both known and predicted genes.

Bivariate genetic association of KIAA1797 with heart rate in American Indians: the Strong Heart Family Study.

Heart rate (HR) has been identified as a risk factor for cardiovascular disease (CVD), yet little is known regarding genetic factors influencing this phenotype. Previous research in American Indians (AIs) from the Strong Heart Family Study (SHFS) identified a significant quantitative trait locus (QTL) for HR on chromosome 9p21. Genetic association on HR was conducted in the SHFS.

Genome-wide association study of conduct disorder symptomatology.

Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD.

A multimodal assessment of the genetic control over working memory.

Working memory performance is significantly influenced by genetic factors. Here, we assessed genetic contributions to both working memory performance and neuroimaging measures focused on the network of brain regions associated with working memory by using a sample of 467 human participants from extended families. Imaging measures included diffusion tensor imaging indices in major white matter tracts thought to be associated with working memory and structural magnetic resonance imaging measures of frontal and parietal gray matter density.