Genome-wide association study of depressive symptoms in the Hispanic Community Health Study/Study of Latinos.

Although genome-wide association studies (GWAS) have identified several variants linked to depression, few GWAS of non-European populations have been performed. We conducted a genome-wide analysis of depression in a large, population-based sample of Hispanics/Latinos. Data came from 12,310 adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Statistical power and utility of meta-analysis methods for cross-phenotype genome-wide association studies.

Advances in recent genome wide association studies (GWAS) suggest that pleiotropic effects on human complex traits are widespread. A number of classic and recent meta-analysis methods have been used to identify genetic loci with pleiotropic effects, but the overall performance of these methods is not well understood. In this work, we use extensive simulations and case studies of GWAS datasets to investigate the power and type-I error rates of ten meta-analysis methods.

Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study.

Background And Purpose: Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis.

Methods: We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry.

Correction: Phenome-wide heritability analysis of the UK Biobank.

[This corrects the article DOI: 10.1371/journal.pgen.

Psychiatric genetics and the structure of psychopathology.

For over a century, psychiatric disorders have been defined by expert opinion and clinical observation. The modern DSM has relied on a consensus of experts to define categorical syndromes based on clusters of symptoms and signs, and, to some extent, external validators, such as longitudinal course and response to treatment. In the absence of an established etiology, psychiatry has struggled to validate these descriptive syndromes, and to define the boundaries between disorders and between normal and pathologic variation.

Ethical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience.

We examined the Institutional Review Board (IRB) process at 9 academic institutions in the electronic Medical Records and Genomics (eMERGE) Network, for proposed electronic health record-based genomic medicine studies, to identify common questions and concerns. Sequencing of 109 disease related genes and genotyping of 14 actionable variants is being performed in ~28,100 participants from the 9 sites. Pathogenic/likely pathogenic variants in actionable genes are being returned to study participants.

An instability of the standard model of cosmology creates the anomalous acceleration without dark energy.

We identify the condition for smoothness at the centre of spherically symmetric solutions of Einstein's original equations without the cosmological constant or dark energy. We use this to derive a universal phase portrait which describes general, smooth, spherically symmetric solutions near the centre of symmetry when the pressure =0. In this phase portrait, the critical =0 Friedmann space-time appears as a saddle rest point which is unstable to spherical perturbations.

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

Background: Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection.

Psychiatric Genomics: An Update and an Agenda.

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets.

A Cross-Sectional Study of Dietary and Genetic Predictors of Blood Folate Levels in Healthy Young Adults.

Since 1998, the U.S. has mandated folic acid (FA) fortification of certain grain products to reduce the risk of neural tube defects.

Characterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource.

Sleep spindles are characteristic electroencephalogram (EEG) signatures of stage 2 non-rapid eye movement sleep. Implicated in sleep regulation and cognitive functioning, spindles may represent heritable biomarkers of neuropsychiatric disease. Here we characterize spindles in 11,630 individuals aged 4 to 97 years, as a prelude to future genetic studies.

The use of electronic health records for psychiatric phenotyping and genomics.

The widespread adoption of electronic health record (EHRs) in healthcare systems has created a vast and continuously growing resource of clinical data and provides new opportunities for population-based research. In particular, the linking of EHRs to biospecimens and genomic data in biobanks may help address what has become a rate-limiting study for genetic research: the need for large sample sizes. The principal roadblock to capitalizing on these resources is the need to establish the validity of phenotypes extracted from the EHR.

Heritability analysis with repeat measurements and its application to resting-state functional connectivity.

Heritability, defined as the proportion of phenotypic variation attributable to genetic variation, provides important information about the genetic basis of a trait. Existing heritability analysis methods do not discriminate between stable effects (e.g.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h) for European-American females of 29% that is similar to h for schizophrenia and is substantially higher than h in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder.

Phenome-wide heritability analysis of the UK Biobank.

Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an upper bound for the utility of genetic risk prediction models. Recent technological and statistical advances have enabled the estimation of additive heritability attributable to common genetic variants (SNP heritability) across a broad phenotypic spectrum. Here, we present a computationally and memory efficient heritability estimation method that can handle large sample sizes, and report the SNP heritability for 551 complex traits derived from the interim data release (152,736 subjects) of the large-scale, population-based UK Biobank, comprising both quantitative phenotypes and disease codes.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects.

Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks.

Genetic risk variants for social anxiety.

Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extraversion.

Anxiety genetics: Dispatches from the frontier.

Anxiety disorders are the most common class of psychiatric disorders and incur an enormous burden in terms of economic costs, disability and personal suffering. Despite their public health importance and documented heritability, genetic research aimed at identifying the genetic contributions to these disorders has had limited success, particularly in comparison to recent advances in the genetics of other major psychiatric disorders. The major factor contributing to this lagging progress has been a dearth of well-powered genomic studies.