Disentangling the complexity of psoriasis in the post-genome-wide association era.

In recent years, genome-wide association studies (GWAS) have been instrumental in unraveling the genetic architecture of complex diseases, including psoriasis. The application of large-scale GWA studies in psoriasis has illustrated several associated loci that participate in the cutaneous inflammation, however explaining a fraction of the disease heritability. With the advent of high-throughput sequencing technologies and functional genomics approaches, the post-GWAS era aims to unravel the functional mechanisms underlying the inter-individual variability in psoriasis patients. In this review, we present the key advances of psoriasis GWAS in under-represented populations, rare, non-coding and structural variants and epistatic phenomena that orchestrate the interplay between different cell types. We further review the gene-gene and gene-environment interactions contributing to the disease predisposition and development of comorbidities through Mendelian randomization studies and pleiotropic effects of psoriasis-associated loci. We finally examine the holistic approaches conducted in psoriasis through system genetics and state-of-the-art transcriptomic analyses, discussing their potential implication in the expanding field of precision medicine and characterization of comorbidities.

Prevalence and Determinants of Sex-Specific Dietary Supplement Use in a Greek Cohort.

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value = 4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR = 0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men.

Cigarette Smoking, Coffee Consumption, Alcohol Intake, and Risk of Crohn's Disease and Ulcerative Colitis: A Mendelian Randomization Study.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are widely associated with smoking in epidemiological studies, whereas there are conflicting results for the association between CD and UC for both coffee and alcohol consumption. Herein, we aimed to investigate whether cigarette smoking and alcohol and coffee consumption are causally associated with either CD or UC. METHODS: We utilized 540 genome-wide significant single-nucleotide polymorphisms for 3 potentially addictive substances-nicotine, alcohol, and caffeine-to assess the association of smoking, coffee, and alcohol consumption with CD and UC (12,194 CD cases, 12,366 UC cases, and 25,042 controls of European ancestry), using Mendelian randomization analysis. Mendelian randomization estimates were used to evaluate the effect of the exposure factors on CD and UC risk. Sensitivity analysis was employed to test for any directional pleiotropy. RESULTS: We found evidence for a positive causal association between the age of smoking initiation and UC risk and between alcohol consumption and CD risk, which disappeared after sensitivity analysis for both associations (P > 0.05). No evidence for a causal association between cigarettes per day, smoking initiation, smoking cessation, and coffee consumption variables and UC or CD was found. CONCLUSIONS: We found no clear evidence that either genetically predicted smoking, coffee consumption, or alcohol consumption are causally associated with the risk for CD or UC, although our findings indicate a potential positive association between the age of smoking and UC and between alcohol consumption and CD.

Comprehensive field synopsis and systematic meta-analyses of genetic association studies in cutaneous melanoma.

BACKGROUND: Although genetic studies have reported a number of loci associated with cutaneous melanoma (CM) risk, a comprehensive synopsis of genetic association studies published in the field and systematic meta-analysis for all eligible polymorphisms have not been reported. METHODS: We systematically annotated data from all genetic association studies published in the CM field (n = 145), including data from genome-wide association studies (GWAS), and performed random-effects meta-analyses across all eligible polymorphisms on the basis of four or more independent case-control datasets in the main analyses. Supplementary analyses of three available datasets derived from GWAS and GWAS-replication studies were also done. Nominally statistically significant associations between polymorphisms and CM were graded for the strength of epidemiological evidence on the basis of the Human Genome Epidemiology Network Venice criteria. All statistical tests were two-sided. RESULTS: Forty-two polymorphisms across 18 independent loci evaluated in four or more datasets including candidate gene studies and available GWAS data were subjected to meta-analysis. Eight loci were identified in the main meta-analyses as being associated with a risk of CM (P < .05) of which four loci showed a genome-wide statistically significant association (P < 1 × 10(-7)), including 16q24.3 (MC1R), 20q11.22 (MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the cumulative evidence by the Venice criteria suggested strong epidemiological credibility for all four loci with genome-wide statistical significance and one additional gene at 9p23 (TYRP1). In the supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached genome-wide statistical significance with CM and had strong epidemiological credibility. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive field synopsis and systematic meta-analysis to identify genes associated with an increased susceptibility to CM.