Expressive

rs11176001 - HMGA2 - MIR6074

Magnitude 2.0 · 7 studies on file

Reported associations

  • 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%

  • Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease - Gut (2025) · Zheng T, Ellinghaus D, Juzenas S, Cossais F, Burmeister G, Mayr G, Jørgensen IF, Teder-Laving M, Skogholt AH, Chen S, Strege PR, Ito G, Banasik K, Becker T, Bokelmann F, Brunak S, Buch S, Clausnitzer H, Datz C, Degenhardt F, Doniec M, Erikstrup C, Esko T, Forster M, Frey N, Fritsche LG, Gabrielsen ME, Gräßle T, Gsur A, Gross J, Hampe J, Hendricks A, Hinz S, Hveem K, Jongen J, Junker R, Karlsen TH, Hemmrich-Stanisak G, Kruis W, Kupcinskas J, Laubert T, Rosenstiel PC, Röcken C, Laudes M, Leendertz FH, Lieb W, Limperger V, Margetis N, Mätz-Rensing K, Németh CG, Ness-Jensen E, Nowak-Göttl U, Pandit A, Pedersen OB, Peleikis HG, Peuker K, Rodriguez CL, Rühlemann MC, Schniewind B, Schulzky M, Skieceviciene J, Tepel J, Thomas L, Uellendahl-Werth F, Ullum H, Vogel I, Volzke H, von Fersen L, von Schönfels W, Vanderwerff B, Wilking J, Wittig M, Zeissig S, Zobel M, Zawistowski M, Vacic V, Sazonova O, Noblin ES, Farrugia G, Beyder A, Wedel T, Kahlke V, Schafmayer C, D'Amato M, Franke A · PubMed 33888516

    ABSTRACT: Objective Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. Design We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in H

  • Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups - Nature genetics (2025) · Hoffmann TJ, Graff RE, Madduri RK, Rodriguez AA, Cario CL, Feng K, Jiang Y, Wang A, Klein RJ, Pierce BL, Eggener S, Tong L, Blot W, Long J, Goss LB, Darst BF, Rebbeck T, Lachance J, Andrews C, Adebiyi AO, Adusei B, Aisuodionoe-Shadrach OI, Fernandez PW, Jalloh M, Janivara R, Chen WC, Mensah JE, Agalliu I, Berndt SI, Shelley JP, Schaffer K, Machiela MJ, Freedman ND, Huang WY, Li SA, Goodman PJ, Till C, Thompson I, Lilja H, Ranatunga DK, Presti J, Van Den Eeden SK, Chanock SJ, Mosley JD, Conti DV, Haiman CA, Justice AC, Kachuri L, Witte JS · PubMed 39930085

    ABSTRACT: We conducted a multiancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry, 58,236 African ancestry, 23,546 Hispanic/Latino and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (P ≤ 5 × 10−8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n = 95,768). Meta-analyzing discovery and replication (n = 392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic

  • GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome - Cell genomics (2025) · Bonfiglio F, Liu X, Smillie C, Pandit A, Kurilshikov A, Bacigalupe R, Zheng T, Nim H, Garcia-Etxebarria K, Bujanda L, Andreasson A, Agreus L, Walter S, Abecasis G, Eijsbouts C, Jostins L, Parkes M, Hughes DA, Timpson N, Raes J, Franke A, Kennedy NA, Regev A, Zhernakova A, Simren M, Camilleri M, D'Amato M · PubMed 34957435

    ABSTRACT: Summary Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10−8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndro

  • Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models. - Nature genetics (2023) · Cosentino J, Behsaz B, Alipanahi B, McCaw ZR, Hill D, Schwantes-An TH, Lai D, Carroll A, Hobbs BD, Cho MH, McLean CY, Hormozdiari F · PubMed 37069358

    Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is highly heritable. While COPD is clinically defined by applying thresholds to summary measures of lung function, a quantitative liability score has more power to identify genetic signals. Here we train a deep convolutional neural network on noisy self-reported and International Classification of Diseases labels to predict COPD case-control status from high-dimensional raw spirograms and use the model's predictions as a liability score. The machine-learning-based (ML-based) liability score accurately discriminates COPD cases and controls, and predicts COPD-related hospitalization without any domain-specific knowledge. Moreover, the ML-based liability score is associated with overall survival and exac

  • 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

  • New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. - Nature genetics (2019) · Shrine N, Guyatt AL, Erzurumluoglu AM, Jackson VE, Hobbs BD, Melbourne CA, Batini C, Fawcett KA, Song K, Sakornsakolpat P, Li X, Boxall R, Reeve NF, Obeidat M, Zhao JH, Wielscher M, Weiss S, Kentistou KA, Cook JP, Sun BB, Zhou J, Hui J, Karrasch S, Imboden M, Harris SE, Marten J, Enroth S, Kerr SM, Surakka I, Vitart V, Lehtimäki T, Allen RJ, Bakke PS, Beaty TH, Bleecker ER, Bossé Y, Brandsma CA, Chen Z, Crapo JD, Danesh J, DeMeo DL, Dudbridge F, Ewert R, Gieger C, Gulsvik A, Hansell AL, Hao K, Hoffman JD, Hokanson JE, Homuth G, Joshi PK, Joubert P, Langenberg C, Li X, Li L, Lin K, Lind L, Locantore N, Luan J, Mahajan A, Maranville JC, Murray A, Nickle DC, Packer R, Parker MM, Paynton ML, Porteous DJ, Prokopenko D, Qiao D, Rawal R, Runz H, Sayers I, Sin DD, Smith BH, Soler Artigas M, Sparrow D, Tal-Singer R, Timmers PRHJ, Van den Berge M, Whittaker JC, Woodruff PG, Yerges-Armstrong LM, Troyanskaya OG, Raitakari OT, Kähönen M, Polašek O, Gyllensten U, Rudan I, Deary IJ, Probst-Hensch NM, Schulz H, James AL, Wilson JF, Stubbe B, Zeggini E, Jarvelin MR, Wareham N, Silverman EK, Hayward C, Morris AP, Butterworth AS, Scott RA, Walters RG, Meyers DA, Cho MH, Strachan DP, Hall IP, Tobin MD, Wain LV · PubMed 30804560

    ABSTRACT: Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent patient populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for C

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