Expressive

rs11125803 - ADCY3

Magnitude 2.0 · 4 studies on file

Reported associations

  • Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Nature communications (2025) · Schoeler T, Pingault JB, Kutalik Z · PubMed 40374629

    ABSTRACT: Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up with LD-score regression and Mendelian Randomization (MR) analyses. Focusing on global cognitive and physical function, we observed marked differences between baseline function (θ) and accelerated decline (Δ). Both outcomes showed distinct heritability levels (e.g., 31.38% versus 3.15%

  • A scalable variational inference approach for increased mixed-model association power - Nature genetics (2025) · Loya H, Kalantzis G, Cooper F, Palamara PF · 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%

  • Multiple Sclerosis Genomic Map implicates peripheral immune cells & microglia in susceptibility - Science (New York, N.Y.) (2020) · Unknown authors · PubMed 31604244

    ABSTRACT: We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observe enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggere

  • 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

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