Huntingtin gene repeat size variations affect risk of lifetime depression.

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons.

Effect of APOE ε4 allele on survival and fertility in an adverse environment.

Background: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4).

The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene.

Background: The oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend these findings, we examined whether three literature-based OXTR SNPs (rs2254298, rs53576, rs2268498) interact with childhood maltreatment in the development of clinically diagnosed depression and anxiety disorders.

KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.

Novel genetic loci underlying human intracranial volume identified through genome-wide association.

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals.

The association between personality traits, cognitive reactivity and body mass index is dependent on depressive and/or anxiety status.

Objective: A range of biological, social and psychological factors, including depression and anxiety disorders, is thought to be associated with higher body mass index (BMI). Depression and anxiety disorders are associated with specific psychological vulnerabilities, like personality traits and cognitive reactivity, that may also be associated with BMI. The relationship between those psychological vulnerabilities and BMI is possibly different in people with and without depression and anxiety disorders.

Heritability of high sugar consumption through drinks and the genetic correlation with substance use.

Background: High sugar consumption contributes to the rising prevalence of obesity. Sugar can have rewarding effects that are similar to, but less strong than, the effects of addictive substances. People who consume large amounts of sugar also tend to use more addictive substances, but it is unclear whether this is due to shared genetic or environmental risk factors.

Depression and cardiovascular disease: Epidemiological evidence on their linking mechanisms.

Depression's burden of disease goes beyond functioning and quality of life and extends to somatic health. Results from longitudinal cohort studies converge in illustrating that major depressive disorder (MDD) subsequently increases the risk of cardiovascular morbidity and mortality with about 80%. The impact of MDD on cardiovascular health may be partly explained by mediating mechanisms such as unhealthy lifestyle (smoking, excessive alcohol use, physical inactivity, unhealthy diet, therapy non-compliance) and unfavorable pathophysiological disturbances (autonomic, HPA-axis, metabolic and immuno-inflammatory dysregulations).

Borderline personality features in depressed or anxious patients.

Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety.

Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank.

People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences.

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels.

Background: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels.

Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression.

Background: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD.

Methods: The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663).

Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression.

Background: Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood.

Serum biomarkers predictive of depressive episodes in panic disorder.

Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA).

Fine mapping the region reveals a common intronic insertion associated to HDL-C.

Background: Individuals with exceptional longevity and their offspring have significantly larger high-density lipoprotein concentrations (HDL-C) particle sizes due to the increased homozygosity for the I405V variant in the cholesteryl ester transfer protein ( gene. In this study, we investigate the association of and HDL-C further to identify novel, independent variants associated with HDL-C in humans.

Methods: We performed a meta-analysis of HDL-C within the region using 59,432 individuals imputed with 1000 Genomes data.