Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation.

Loneliness is a complex biological trait that has been associated with numerous negative health outcomes. The measurement and environmental determinants of loneliness are well understood, but its genetic basis is not. Previous studies have estimated the heritability of loneliness between 37 and 55% using twins and family-based approaches, and have explored the role of specific candidate genes.

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts.

Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

Background: Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci.

Inter-observer reliability of DSM-5 substance use disorders.

Aims: Although studies have examined the impact of changes made in DSM-5 on the estimated prevalence of substance use disorder (SUD) diagnoses, there is limited evidence concerning the reliability of DSM-5 SUDs. We evaluated the inter-observer reliability of four DSM-5 SUDs in a sample in which we had previously evaluated the reliability of DSM-IV diagnoses, allowing us to compare the two systems.

Methods: Two different interviewers each assessed 173 subjects over a 2-week period using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA).

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

Importance: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).

Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations.

Rationale: Researchers studying behavioral and physiologic effects of d-amphetamine have explored individual response differences to the drug. Concurrently, genome-wide analyses have identified several single-nucleotide polymorphisms (SNPs) associated with these traits. Univariate methods can identify SNPs associated with behavioral and physiological traits, but multivariate analyses allow identification of clusters of related biologically relevant SNPs and behavioral components.

Which alcohol use disorder criteria contribute to the association of ADH1B with alcohol dependence?

Although alcohol dependence (AD) is approximately 50% heritable, little is known about how specific genetic loci affect AD risk. In a genome-wide association study (GWAS), we identified highly significant associations between two population-specific functional variants in the alcohol dehydrogenase 1B gene (ADH1B) and AD in African-Americans (AAs; rs2066702) and European-Americans (EAs; rs1229984). In the current study, we determined which specific diagnostic criteria contributed to the observed associations of ADH1B SNPs with AD.

Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.

Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ≤ 0.05 and P ≤ 0.

Psychopharmacology of theobromine in healthy volunteers.

Background: Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited.

Objectives: We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants.

Candidate gene studies of a promising intermediate phenotype: failure to replicate.

Many candidate gene studies use 'intermediate phenotypes' instead of disease diagnoses. It has been proposed that intermediate phenotypes have simpler genetic architectures such that individual alleles account for a larger percentage of trait variance. This implies that smaller samples can be used to identify genetic associations.

Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).

Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers.

Genetic factors modulating the response to stimulant drugs in humans.

Individuals vary in their responses to stimulant drugs, and several lines of evidence suggest that the basis for this variation is at least partially genetic in origin. Association studies have examined the effects of polymorphisms in specific genes on acute and chronic responses to stimulant drugs. Several of these genetic polymorphisms are also associated with other psychiatric dimensions and disorders.