Expressive

rs12147845 - LINC00523 - DLK1

Magnitude 2.0 · 8 studies on file

Reported associations

  • Leveraging Polygenic Functional Enrichment to Improve GWAS Power. - American journal of human genetics (2019) · Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL · PubMed 30595370

    Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, functionally informed novel discovery of risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9%-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N = 130K). Averaged across traits, we attaine

  • Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood - Unknown journal (n.d.) · Unknown authors · PubMed 37280435

    ABSTRACT: Aims/hypothesis Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical. Methods By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity. Results We found tha

  • Participation bias in the UK Biobank distorts genetic associations and downstream analyses - Unknown journal (n.d.) · Unknown authors · PubMed 37106081

    ABSTRACT: While volunteer-based studies such as the UK Biobank have become the cornerstone of genetic epidemiology, the participating individuals are rarely representative of their target population. To evaluate the impact of selective participation, here we derived UK Biobank participation probabilities on the basis of 14 variables harmonized across the UK Biobank and a representative sample. We then conducted weighted genome-wide association analyses on 19 traits. Comparing the output from weighted genome-wide association analyses (neffective = 94,643 to 102,215) with that from standard genome-wide association analyses (n = 263,464 to 283,749), we found that increasing representativeness led to changes in SNP effect sizes and identified novel SNP associations for 12 traits. While

  • A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

    ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

  • A Genomics England haplotype reference panel and imputation of UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 39134668

    ABSTRACT: We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r2 = 0.75 for variants with minor allele frequencies as low as 2 × 10−4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10−11), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants. A Genomics England haplotype reference panel constructed using sequence data from 78,195 individuals

  • Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study - Unknown journal (n.d.) · Unknown authors · PubMed 32376654

    ABSTRACT: Abstract Objective To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood. Design Two sample univariable and multivariable mendelian randomisation. Setting The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums. Participants 453 169 participants enrolled in UK Biobank and a combined total of more than 700 000 people from different GWAS consortiums. Exposures Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10. Main outcome measures Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer. Results Having a larger genetically predicted body

  • Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry - Unknown journal (n.d.) · Unknown authors · PubMed 30239722

    ABSTRACT: Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR

  • Pleiotropic genetic architecture and novel loci for C-reactive protein levels - Unknown journal (n.d.) · Unknown authors · PubMed 36376304

    ABSTRACT: C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci, we perform multi-trait analysis of genome-wide association studies on C-reactive protein levels along with cardiometabolic traits, followed by a series of in silico analyses including colocalization, phenome-wide association studies and Mendelian randomization. We find 41 novel loci and 19 gene sets associated with C-reactive protein with various pleiotropic effects. Additionally, 41 variants colocalize between C-reactive protein and cardiometabolic risk factors and 12 of them display

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