A SNP, Gene, and Polygenic Risk Score Approach of Oxytocin-Vasopressin Genes in Adolescents' Loneliness.

Not much is known regarding underlying biological pathways to adolescents' loneliness. Insight in underlying molecular mechanisms could inform intervention efforts aimed at reducing loneliness. Using latent growth curve modeling, baseline levels and development of loneliness were studied in two longitudinal adolescent samples. Genes (OXTR, OXT, AVPR1A, AVPR1B) were examined using SNP-based, gene-based, and polygenic risk score (PRS) approaches. In both samples, SNP- and gene-based tests showed involvement of the OXTR gene in development of loneliness, though, significance levels did not survive correction for multiple testing. The PRS approach provided no evidence for relations with loneliness. We recommend alternative phenotyping methods, including environmental factors, to consider epigenetic studies, and to examine possible endophenotypes in relation to adolescents' loneliness.

A genetic analysis of coffee consumption in a sample of Dutch twins.

Caffeine is by far the most commonly used psychoactive substance. Caffeine is consumed regularly as an ingredient of coffee. Coffee consumption and coffee preference was explored in a sample of 4,495 twins (including 1,231 pairs) registered with the Netherlands Twin Registry. Twin resemblance was assessed by tetrachoric correlations and the influence of both genetic and environmental factors was explored with model fitting analysis in MX. Results showed moderate genetic influences (39%) on coffee consumption. The remaining variance was explained by shared environmental factors (21%) and unique environmental factors (40%). The variance in coffee preference (defined as the proportion of coffee consumption relative to the consumption of coffee and tea in total) was explained by genetic factors (62%) and unique environmental factors (38%).

Relevance of positive patch-test reactions to fragrance mix.

BACKGROUND: Fragrances are an important cause of allergic contact dermatitis. We presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance-allergic patients. FM has an irritant potential. Weak positive reactions may have a greater chance of being irrelevant than strong reactions. OBJECTIVE: To improve the appraisal of FM patch-test reactions, we studied the relevance of reactions of different strength. We also studied the predictive value of the following on the relevance of the initial FM patch-test results: patch-test results of a repeated FM test; results of patch tests with balsam of Peru, colophony, and ingredients of the mix; and (history of) atopic dermatitis. METHODS: One hundred thirty-eight patients who had doubtful positive (?+) or positive (+ to +++) reactions were included in the study. We determined relevance by history taking, location and course of the dermatitis, and additional patch testing. Patients were retested with FM and with each ingredient separately. RESULTS: The relevance of reactions to FM increases with the strength of the reactions. Predictors of relevance are the results of retesting with FM, the results of tests with the ingredients, and a history and/or present symptoms of atopic dermatitis. CONCLUSION: Retesting with FM and its ingredients may add to the benefit of patch testing.

Role of nicotine dependence in the association between the dopamine receptor gene DRD3 and major depressive disorder.

BACKGROUND: The aims of this study were to analyze associations of dopamine receptor genes (DRD1-5) with Major Depressive Disorder (MDD) and nicotine dependence (ND), and to investigate whether ND moderates genetic influences on MDD. METHODS: The sample was ascertained from the Finnish Twin Cohort. Twin pairs concordant for smoking history were recruited along with their family members, as part of the multisite Nicotine Addiction Genetics consortium. Genetic association analyses were based on 1428 adults. Total of 70 tagging single nucleotide polymorphisms within the dopamine receptor genes were genotyped and analyzed for association with MDD, ND, and MD-ND co-morbidity. Individual level logistic regression analyses were based on 1296 adults with data on ND and MDD diagnoses, as well as on dopamine receptor genotypes adjusted for sex, age, and alcohol use. Four independent samples, such as population-based and case-control samples, were used for replication. RESULTS: Rs2399496, located 1.5 kb downstream of DRD3, showed suggestive association for MDD (p = 0.00076) and significant association for MDD-ND co-morbidity (p = 0.000079). Suggestive gene-(rs2399496) by-ND-interaction justified analyses by genetic risk variant and ND status. Individuals with ND and two minor alleles (AA) of rs2399496 had almost six-fold risk for MDD (OR 5.74, 95%CI 3.12-10.5, p = 9.010e-09) compared to individuals without ND and with two major alleles (TT). CONCLUSIONS: Significant association between a variant downstream of DRD3 and a co-morbid MDD-ND phenotype was detected. Our results further suggest that nicotine dependence may potentiate the influence of the DRD3 genetic variant on MDD.