Developing community-based health education strategies with family history: Assessing the association between community resident family history and interest in health education.

Background: Family history (FH) is an underutilized genetically informative tool that can influence disease prevention and treatment. It is unclear how FH fits into the development of community-based health education. This study examines the role that FH plays in perceived threat and health education related to mental and chronic physical conditions in the context of the health belief model.

Comparison of cardiometabolic risk biomarkers from a national clinical laboratory with the US adult population.

Background: Clinical laboratory patient databases are an untapped source of valuable diagnostic and prognostic information. However, the lack of associated clinical and/or demographic information and questionable generalizability to nonpatient populations often limit utility of these data.

Objectives: This study compared levels of cardiometabolic biomarkers between a national clinical laboratory patient cohort (Health Diagnostic Laboratory [HD Lab]) and the US population as inferred from the National Health and Nutrition Examination Survey (NHANES, 2011-2012).

Biomarkers of cholesterol homeostasis in a clinical laboratory database sample comprising 667,718 patients.

Background: Circulating noncholesterol sterols/stanols (NCS) are used in clinical lipidology as surrogate measures of cholesterol synthesis and absorption, where they can be valuable tools in assessing cholesterol metabolism and personalizing therapies in patients with dyslipidemia.

Objectives: To describe the distributions of plasma NCS concentrations and inter-NCS correlations in a large cohort of American patients constituting a clinical laboratory database, and to investigate the relationship between circulating NCS, age, sex, and apolipoprotein E (APOE) genotype.

Methods: A total of 667,718 patient blood samples submitted for testing to Health Diagnostic Laboratory, Inc.

Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes.

Background: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes.

Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice.

Background: Discordance between measures of atherogenic lipoprotein particle number (apolipoprotein B [ApoB] and low-density lipoprotein [LDL] particle number by nuclear magnetic resonance spectroscopy [LDL-PNMR]) is not well understood. Appropriate treatment considerations in such cases are unclear.

Objectives: To assess discordance between apoB determined by immunoassay and LDL-PNMR in routine clinical practice, and to characterize biomarker profiles and other clinical characteristics of patients identified as discordant.

Lipoprotein(a) mass: a massively misunderstood metric.

The importance of lipoprotein (a)-Lp(a)-as a cardiovascular (CV) risk marker has been underscored by recent findings that CV risk is directly related to baseline Lp(a) levels, even in well-treated patients. Although there is currently little that can be done pharmacologically to lower Lp(a) levels, knowledge of its serum concentration is important in overall risk assessment. This review focuses on 1 aspect of Lp(a) that is rarely discussed directly: how to express its levels in serum.

Serum α-hydroxybutyrate (α-HB) predicts elevated 1 h glucose levels and early-phase β-cell dysfunction during OGTT.

Objective: Serum α-hydroxybutyrate (α-HB) is elevated in insulin resistance and diabetes. We tested the hypothesis that the α-HB level predicts abnormal 1 h glucose levels and β-cell dysfunction inferred from plasma insulin kinetics during a 75 g oral glucose tolerance test (OGTT).

Research Design And Methods: This cross-sectional study included 217 patients at increased risk for diabetes.

Validation of a lipoprotein(a) particle concentration assay by quantitative lipoprotein immunofixation electrophoresis.

Background: Low-density lipoprotein (LDL) particle (P, or molar) concentration has been shown to be a more sensitive marker of cardiovascular disease (CVD) risk than LDL cholesterol. Although elevated circulating lipoprotein(a) [Lp(a)] cholesterol and mass have been associated with CV risk, no practicable method exists to measure Lp(a)-P. We have developed a method of determining Lp(a)-P suitable for routine clinical use.

Clinical and molecular genetic findings in autosomal dominant OPA3-related optic neuropathy.

Leber hereditary optic neuropathy and autosomal dominant optic atrophy are the two most common inherited optic neuropathies. The latter has been associated with mutations in the OPA1 and OPA3 genes. To date, only six families with OPA3-associated dominant optic atrophy have been reported.

Comprehensive biomarker testing of glycemia, insulin resistance, and beta cell function has greater sensitivity to detect diabetes risk than fasting glucose and HbA1c and is associated with improved glycemic control in clinical practice.

Blood-based biomarker testing of insulin resistance (IR) and beta cell dysfunction may identify diabetes risk earlier than current glycemia-based approaches. This retrospective cohort study assessed 1,687 US patients at risk for cardiovascular disease (CVD) under routine clinical care with a comprehensive panel of 19 biomarkers and derived factors related to IR, beta cell function, and glycemic control. The mean age was 53 ± 15, 42 % were male, and 25 % had glycemic indicators consistent with prediabetes.

Does APOE genotype modify the relations between serum lipid and erythrocyte omega-3 fatty acid levels?

Earlier reports indicated that patients with the apolipoprotein APOE ε4 allele responded to fish oil supplementation with a rise in serum low-density lipoprotein cholesterol (LDL-C) compared to ε3 homozygotes. In this study, we used clinical laboratory data to test the hypothesis that the cross-sectional relation between RBC omega-3 fatty acid status (the Omega-3 Index) and LDL-C was modified by APOE genotype. Data from 136,701 patients were available to compare lipid biomarker levels across Omega-3 Index categories associated with heart disease risk in all APOE genotypes.

An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis.

Identifying rare, highly penetrant risk mutations may be an important step in dissecting the molecular etiology of schizophrenia. We conducted a gene-based analysis of large (>100 kb), rare copy-number variants (CNVs) in the Wellcome Trust Case Control Consortium 2 (WTCCC2) schizophrenia sample of 1564 cases and 1748 controls all from Ireland, and further extended the analysis to include an additional 5196 UK controls. We found association with duplications at chr20p12.

Association study of 167 candidate genes for schizophrenia selected by a multi-domain evidence-based prioritization algorithm and neurodevelopmental hypothesis.

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n=3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain.

Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23).

X-linked retinitis pigmentosa (XLRP) is genetically heterogeneous with two causative genes identified, RPGR and RP2. We previously mapped a locus for a severe form of XLRP, RP23, to a 10.71 Mb interval on Xp22.

Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

Background: Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.

Methods: We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects).

The AVPR1A gene and substance use disorders: association, replication, and functional evidence.

Background: The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.

Methods: In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).

Results: Associations (p ≤ .

AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families.

Background: The phosphatidylinositol 3-kinase (PI3K)-AKT signal transduction pathway is critical to cell growth and survival. In vitro functional studies indicate that the candidate schizophrenia susceptibility gene DTNBP1 influences AKT signaling to promote neuronal viability. The AKT1 gene has also been implicated in schizophrenia by association studies and decreased protein expression in the brains of schizophrenic patients.

Identification of susceptibility loci for alcohol-related traits in the Irish Affected Sib Pair Study of Alcohol Dependence.

Background: Alcoholism is a phenotypically and probably genetically heterogeneous condition. Thus, one strategy for finding genes influencing liability to alcoholism is to study the components of alcoholism, which may be more directly related to the underlying pathophysiology than is clinical diagnosis. The goal of this study was to identify genomic regions containing susceptibility loci for alcohol-related traits.

A comprehensive survey of mutations in the OPA1 gene in patients with autosomal dominant optic atrophy.

Purpose: To characterize the spectrum of mutations in the OPA1 gene in a large international panel of patients with autosomal dominant optic atrophy (adOA), to improve understanding of the range of functional deficits attributable to sequence variants in this gene, and to assess any genotype-phenotype correlations.

Methods: All 28 coding exons of OPA1, intron-exon splice sites, 273 bp 5' to exon 1, and two intronic regions with putative function were screened in 94 apparently unrelated white patients of European origin with adOA by single-strand conformational polymorphism (SSCP)-heteroduplex analysis and direct sequencing. Clinical data were collated, and putative mutations were tested for segregation in the respective families by SSCP analysis or direct sequencing and in 100 control chromosomes.

An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders.

Human chromosome Xp11.3-Xp11.23 encompasses the map location for a growing number of diseases with a genetic basis or genetic component.

A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene.

Normal tension glaucoma (NTG) is a major form of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. OPA1, the gene responsible for autosomal dominant optic atrophy represents an excellent candidate gene for NTG, as the clinical phenotypes are similar and OPA1 is expressed in the retina and optic nerve. Eighty-three well-characterized NTG patients were screened for mutations in OPA1 by heteroduplex analysis and bi-directional sequencing.