Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects ≈1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study meta-analysis was 2.4 × 10 ⁻⁶ . We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P ≈ 10 ⁻⁷ : 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 ( MCTP1 ). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, P = 1.8 × 10 ⁻⁷ ) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3 , NEK4 , and ITIH3 . Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, P = 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10⁻⁶) and GPC6 showed suggestive evidence for interaction with age (p≈10⁻⁷). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.

Colorectal cancer (CRC) is one of the most prevalent cancers affecting humans, with a complex genetic and environmental aetiology. Unlike cancers with known environmental, heritable, or sex-linked causes, sporadic CRC is hard to foresee and has no molecular biomarkers of risk in clinical use. One in twenty CRC cases presents with an established heritable component. The remaining cases are sporadic and associated with partially obscure genetic, epigenetic, regenerative, microbiological, dietary, and lifestyle factors. To tackle this complexity, we should improve the practice of colonoscopy, which is recommended uniformly beyond a certain age, to include an assessment of biomarkers indicative of individual CRC risk. Ideally, such biomarkers will be causal to the disease and potentially modifiable upon dietary or therapeutic interventions. Multi-omics analysis, including transcriptional, epigenetic as well as metagenomic, and metabolomic profiles, are urgently required to provide data for risk analyses. The aim of this article is to provide a perspective on the multifactorial derailment of homeostasis leading to the initiation of CRC, which may be explored via multi-omics and Gut-on-Chip analysis to identify much-needed predictive biomarkers.

The aim of our study was to evaluate the potential association between physical activity and occupational stress among firefighters. Data were collected from Cypriot firefighters through a web-based battery of internationally validated questionnaires completed anonymously (COPSOQ, DASS). A total of 430 firefighters (response rate 68%) completed the survey (age range: 21–60 years). More than half of the firefighters (54%) reported either no or minimal physical activity. A total of 11% of firefighters reported moderate to extremely severe stress based on the DASS-S scale. Using multivariable-adjusted logistic regression models, we showed that firefighters who exercised had 50% lower risk of occupational stress, and using a categorical model, we found that every hour per week of increased physical activity among firefighters was associated with 16% lower risk of occupational stress after adjusting for age, education, smoking, and body mass index (OR = 1.16; p = 0.05). In addition, our findings suggest an inverse dose–response relationship between physical activity and occupational stress among firefighters. Physical activity appears to be inversely associated with occupational stress and serves as an important mitigating factor of occupational stress in firefighters. Further research is warranted to evaluate the potential effect of exercise interventions on occupational stress, and the overall mental health of firefighters and other occupational groups.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet