Evidence for a shared genetic contribution to loneliness and borderline personality disorder.

Loneliness, influenced by genetic and environmental factors such as childhood maltreatment, is one aspect of interpersonal dysfunction in Borderline Personality Disorder (BPD). Numerous studies link loneliness and BPD and twin studies indicate a genetic contribution to this association. The aim of our study was to investigate whether genetic predisposition for loneliness and BPD risk overlap and whether genetic risk for loneliness contributes to higher loneliness reported by BPD patients, using genome-wide genotype data.

Borderline personality disorder and the big five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness.

Both environmental (e.g. interpersonal traumatization during childhood and adolescence) and genetic factors may contribute to the development of Borderline Personality Disorder (BPD).

Elimination Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth) in Blood during Alcohol Detoxification.

Aims: The study documented elimination characteristics of three phosphatidylethanol (PEth) homologs in serially collected blood samples from 47 heavy drinkers during ~2 weeks of alcohol detoxification at hospital.

Methods: Venous whole blood and urine samples were collected every 1-2 days during treatment. Concentrations of PEth, and of urinary ethyl glucuronide (EtG) and ethyl sulfate (EtS) to detect relapse drinking, were measured using liquid chromatography-tandem mass spectrometry.

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280).

Shared genetic etiology between alcohol dependence and major depressive disorder.

The clinical comorbidity of alcohol dependence (AD) and major depressive disorder (MDD) is well established, whereas genetic factors influencing co-occurrence remain unclear. A recent study using polygenic risk scores (PRS) calculated based on the first-wave Psychiatric Genomics Consortium MDD meta-analysis (PGC-MDD1) suggests a modest shared genetic contribution to MDD and AD. Using a (~10 fold) larger discovery sample, we calculated PRS based on the second wave (PGC-MDD2) of results, in a severe AD case–control target sample.

Potential of Oral Fluid as a Clinical Specimen for Compliance Monitoring of Psychopharmacotherapy.

Background: Oral fluid (OF) is being developed as a specimen for the determination of drug intake as an alternative to serum and plasma. It is generally considered as an attractive specimen due to the noninvasive nature of the sampling procedure and the relation to the free fraction of drug in the blood. These features are of particular value in drug treatment of psychiatric disorders.

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted.

Psychiatric Comorbidities in Restless Legs Syndrome.

Restless legs syndrome (RLS) is a neurological sleep disorder with frequent (39%) coexisting psychiatric comorbidities. Patients with any psychiatric comorbidity had fewer periodic leg movements in sleep. Psychiatric disorders should be taken into account in patients with RLS.

Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression--The EMC trial.

Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram.

Replication of the association between CHRNA4 rs1044396 and harm avoidance in a large population-based sample.

Harm avoidance is a personality trait characterized by excessive worrying and fear of uncertainty, which has repeatedly been related to anxiety disorders. Converging lines of research in rodents and humans point towards an involvement of the nicotinic cholinergic system in the modulation of anxiety. Most notably, the rs1044396 polymorphism in the CHRNA4 gene, which codes for the α4 subunit of the nicotinic acetylcholine receptor, has been linked to negative emotionality traits including harm avoidance in a recent study.

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects.

Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder.

The objective of this study was to investigate the hypothesis that borderline personality disorder (BPD) and bipolar disorder (BD) share genetic variation through analysis of known genetic risk factors for BD in a well-characterized BPD case-control cohort. Genotyping of five genome-wide significant variants identified for BD (in CACNA1C, ANK3, and ODZ4) was performed in 673 BPD cases and 748 controls. A nominally significant association with BPD was found for rs1006737 in CACNA1C (P=0.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis.

Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS).

XRCC5 as a risk gene for alcohol dependence: evidence from a genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans.

Genetic factors have as large role as environmental factors in the etiology of alcohol dependence (AD). Although genome-wide association studies (GWAS) enable systematic searches for loci not hitherto implicated in the etiology of AD, many true findings may be missed owing to correction for multiple testing. The aim of the present study was to circumvent this limitation by searching for biological system-level differences, and then following up these findings in humans and animals.

Association between dopa decarboxylase gene variants and borderline personality disorder.

Despite heritability estimates of 37-69%, research has identified few genetic risk variants for borderline personality disorder (BPD). The present collaborative candidate gene study of 987 BPD cases and 1110 healthy controls found an association between BPD and single nucleotide polymorphism rs12718541 in the dopa decarboxylase gene.

A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.

Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages ≤ 51 years. The SNPs with smallest P values were examined in a replication set of 3,470 EOBC cases and 5,475 control women.

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women.

Objective: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution.

The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism.

Rationale: Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence.

Objectives: We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI.

A genomewide association study of smoking relapse in four European population-based samples.

Objectives: Genomewide association studies (GWAS) have identified clear evidence of genetic markers for nicotine dependence. Other smoking phenotypes have been tested, but the results are less consistent. The tendency to relapse versus the ability to maintain long-term abstinence has received little attention in genetic studies; thus, our aim was to provide a better biological understanding of this phenotype through the identification of genetic loci associated with smoking relapse.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS).

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping.

Association of VMAT2 gene polymorphisms with alcohol dependence.

Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA.

αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior.

The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice.