Project description:Pseudoexfoliation syndrome (PEXS) is a late-onset disorder in which fibrillar material accumulates at abnormally high concentrations mainly in the anterior segment of the eye. PEXS is the most common cause of secondary glaucoma, which can ultimately lead to blindness and is associated with a higher risk of cataract and serious complications following different types of intraocular surgery. Although PEXS clearly has a genetic component, it remains poorly explored. In our genome-wide association study, we searched for an association of genetic variants with this disorder among older Poles with PEXS without glaucoma.
Project description:Background: Most skin-related traits have been studied in Caucasian genetic backgrounds. A comprehensive study on skin-associated genetic effects on underrepresented populations such as Vietnam is needed to fill the gaps in the field. Objectives: We aimed to develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole-genome sequencing (WGS) data from the 1000 Genomes Project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). Also, we compared the genetic predispositions of 25 skin-related traits of Vietnamese population to others to acquire population-specific insights regarding skin health. Results: The skin-related genetic profile of Vietnamese cohorts was similar at most to East Asian cohorts (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3)).
Project description:We use targeted bisulfite PCR and next-generation 454 sequencing of multiple amplicons to analyze the association of cis-regulated allele-specific methylation (ASM) with multiple complex disease-associated variants in a population of 82 individuals. We detect ASM at four variants implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn’s disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). 82 samples analysed
Project description:<p>We investigated the cumulative contribution of rare, exonic genetic variants on the concentration of 1,487 metabolites and 53,714 metabolite ratios in urine by performing gene-based tests based on 226,233 variants from up to 4,864 participants of the German Chronic Kidney Disease (GCKD) study. There were 128 significant associations (53 metabolite-gene and 75 metabolite ratio-gene pairs) involving 30 unique genes, 16 of which are known to underlie recessively inherited inborn errors of metabolism (IEMs). Across the 30 genes, 47% of individuals carried at least one rare missense, stop or splice variant. The 30 genes were strongly enriched for shared high expression in liver and kidney (OR=65, p-FDR=3e-7), with hepatocytes and proximal tubule cells as driving cell types. Use of whole-exome sequencing data in the UK Biobank allowed for linking genes to diseases that could plausibly be explained by the identified metabolites. In silico constraint-based modeling of knockouts of the implicated genes in a virtual whole-body, organ-resolved metabolic human correctly predicted the observed direction of metabolite changes in urine and blood, highlighting the potential of linking population genetics to modeling to validate associations and to predict metabolic consequences of yet unknown IEMs. Our study extends the map of genes influencing urine metabolite concentrations, reveals metabolic processes and connected health outcomes, and implicates novel candidate variants and genes for IEMs.</p><p><br></p><p>Further links;</p><p><a href='https://www.gckd.org/' rel='noopener noreferrer' target='_blank'>German Chronic Kidney Disease (GCKD)</a></p>
Project description:In our genome-wide association study, we searched for an association of genetic variants with colorectal cancer, type 1 diabetes, Hodgkin lymphoma and Diffuse large B-cell lymphoma among Polish population.
Project description:Total RNA samples from three independent transfection experiments of vectors containing two different allelic variants of 4 miRNAs (hsa-mir-146a, hsa-mir-196a2, hsa-mir-499a, hsa-mir-499b) and an empty vector. The selected variants are cancer associated SNPs located in cancer related miRNAs. The aim of this study is to identify functional explanations for those associations. HeLa cells were used for microarray expression experiments in Agilent SurePrint G3 Human Gene Expression microarrays (8x60k), which target over 60,000 well-annotated RefSeq transcripts starting from 300ng of total RNA. Data were analyzed using the Array File Maker (AFM) 4.0 software package (Array File Maker, Stanford, California).
Project description:Schizophrenia (SCZ) is a highly polygenic disease and genome wide association studies have identified thousands of genetic variants that are statistically associated with this psychiatric disorder. However, our ability to translate these associations into insights on the disease mechanisms has been challenging since the causal genetic variants, their molecular function and their target genes remain largely unknown. In order to address these questions, we established a functional genomics pipeline in combination with induced pluripotent stem cell technology to functionally characterize 35,000 non-coding genetic variants associated with schizophrenia along with their target genes. This analysis identified a set of 620 (1.7%) single nucleotide polymorphisms as functional on a molecular level in a highly cell type and condition specific fashion. These results provide a high-resolution map of functional variant-gene combinations and offer comprehensive biological insights into the developmental context and stimulation dependent molecular processes modulated by SCZ associated genetic variation.