BackgroundGenome-wide association studies (GWAS) are an important method for mapping genetic variation underlying complex traits and diseases. Tools to visualize, annotate and analyse results from these studies can be used to generate hypotheses about the molecular mechanisms underlying the associations.FindingsThe Complex-Traits Genetics Virtual Lab (CTG-VL) integrates over a thousand publicly-available GWAS summary statistics, a suite of analysis tools, visualization functions and diverse data sets for genomic annotations. CTG-VL also makes available results from gene, pathway and tissue-based analyses from over 1,500 complex-traits allowing to assess pleiotropy not only at the genetic variant level but also at the gene, pathway and tissue levels. In this manuscript, we showcase the platform by analysing GWAS summary statistics of mood swings derived from UK Biobank. Using analysis tools in CTG-VL we highlight hippocampus as a potential tissue involved in mood swings, and that pathways including neuron apoptotic process may underlie the genetic associations. Further, we report a negative genetic correlation with educational attainment rG = −0.41 ± 0.018 and a potential causal effect of BMI on mood swings OR = 1.01 (95% CI = 1.00–1.02). Using CTG-VL’s database, we show that pathways and tissues associated with mood swings are also associated with neurological traits including reaction time and neuroticism, as well as traits such age at menopause and age at first live birth.ConclusionsCTG-VL is a platform with the most complete set of tools to carry out post-GWAS analyses. The CTG-VL is freely available at https://genoma.io as an online web application.
Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N=5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P=1.04×10−3). Our estimate of the effect of education on myopia was higher (P=0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [~2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error.
Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two
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