Expressive

rs112540634 - ILRUN

Magnitude 2.0 · 8 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%

  • Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes - Nature genetics (2025) · Henry A, Mo X, Finan C, Chaffin MD, Speed D, Issa H, Denaxas S, Ware JS, Zheng SL, Malarstig A, Gratton J, Bond I, Roselli C, Miller D, Chopade S, Schmidt AF, Abner E, Adams L, Andersson C, Aragam KG, Ärnlöv J, Asselin G, Raja AA, Backman JD, Bartz TM, Biddinger KJ, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunak S, Bruun MT, Buckbinder L, Bundgaard H, Carey DJ, Chasman DI, Chen X, Cook JP, Czuba T, de Denus S, Dehghan A, Delgado GE, Doney AS, Dörr M, Dowsett J, Dudley SC, Engström G, Erikstrup C, Esko T, Farber-Eger EH, Felix SB, Finer S, Ford I, Ghanbari M, Ghasemi S, Ghouse J, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Hägg S, Haggerty CM, Hedman ÅK, Helgadottir A, Hemingway H, Hillege H, Hyde CL, Aagaard Jensen B, Jukema JW, Kardys I, Karra R, Kavousi M, Kizer JR, Kleber ME, Køber L, Koekemoer A, Kuchenbaecker K, Lai YP, Lanfear D, Langenberg C, Lin H, Lind L, Lindgren CM, Liu PP, London B, Lowery BD, Luan J, Lubitz SA, Magnusson P, Margulies KB, Marston NA, Martin H, März W, Melander O, Mordi IR, Morley MP, Morris AP, Morrison AC, Morton L, Nagle MW, Nelson CP, Niessner A, Niiranen T, Noordam R, Nowak C, O'Donoghue ML, Ostrowski SR, Owens AT, Palmer CNA, Paré G, Pedersen OB, Perola M, Pigeyre M, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Rotter JI, Ruff CT, Sabatine MS, Sallah N, Salomaa V, Sattar N, Shalaby AA, Shekhar A, Smelser DT, Smith NL, Sørensen E, Srinivasan S, Stefansson K, Sveinbjörnsson G, Svensson P, Tammesoo ML, Tardif JC, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Tragante V, Trompet S, Uitterlinden AG, Ullum H, van der Harst P, van Heel D, van Setten J, van Vugt M, Veluchamy A, Verschuuren M, Verweij N, Vissing CR, Völker U, Voors AA, Wallentin L, Wang Y, Weeke PE, Wiggins KL, Williams LK, Yang Y, Yu B, Zannad F, Zheng C, Asselbergs FW, Cappola TP, Dubé MP, Dunn ME, Lang CC, Samani NJ, Shah S, Vasan RS, Smith JG, Holm H, Shah S, Ellinor PT, Hingorani AD, Wells Q, Lumbers RT · PubMed 40038546

    ABSTRACT: Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been re

  • Femoral neck width genetic risk score is a novel independent risk factor for hip fractures - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2024) · Tobias JH, Nethander M, Faber BG, Heppenstall SV, Ebsim R, Cootes T, Lindner C, Saunders FR, Gregory JS, Aspden RM, Harvey NC, Kemp JP, Frysz M, Ohlsson C · PubMed 38477772

    ABSTRACT: Abstract Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to gene

  • A Genomics England haplotype reference panel and imputation of UK Biobank - Nature genetics (2024) · Shi S, Rubinacci S, Hu S, Moutsianas L, Stuckey A, Need AC, Palamara PF, Caulfield M, Marchini J, Myers S · 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

  • Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer - Science advances (2024) · Peruchet-Noray L, Sedlmeier AM, Dimou N, Baurecht H, Fervers B, Fontvieille E, Konzok J, Tsilidis KK, Christakoudi S, Jansana A, Cordova R, Bohmann P, Stein MJ, Weber A, Bézieau S, Brenner H, Chan AT, Cheng I, Figueiredo JC, Garcia-Etxebarria K, Moreno V, Newton CC, Schmit SL, Song M, Ulrich CM, Ferrari P, Viallon V, Carreras-Torres R, Gunter MJ, Freisling H · PubMed 38640244

    ABSTRACT: It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,77

  • GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer - Scientific reports (2021) · Christakoudi S, Evangelou E, Riboli E, Tsilidis KK · PubMed 34021172

    ABSTRACT: Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to can

  • The Polygenic and Monogenic Basis of Blood Traits and Diseases - Cell (2021) · Vuckovic D, Bao EL, Akbari P, Lareau CA, Mousas A, Jiang T, Chen MH, Raffield LM, Tardaguila M, Huffman JE, Ritchie SC, Megy K, Ponstingl H, Penkett CJ, Albers PK, Wigdor EM, Sakaue S, Moscati A, Manansala R, Lo KS, Qian H, Akiyama M, Bartz TM, Ben-Shlomo Y, Beswick A, Bork-Jensen J, Bottinger EP, Brody JA, van Rooij FJA, Chitrala KN, Wilson PWF, Choquet H, Danesh J, Di Angelantonio E, Dimou N, Ding J, Elliott P, Esko T, Evans MK, Felix SB, Floyd JS, Broer L, Grarup N, Guo MH, Guo Q, Greinacher A, Haessler J, Hansen T, Howson JMM, Huang W, Jorgenson E, Kacprowski T, Kähönen M, Kamatani Y, Kanai M, Karthikeyan S, Koskeridis F, Lange LA, Lehtimäki T, Linneberg A, Liu Y, Lyytikäinen LP, Manichaikul A, Matsuda K, Mohlke KL, Mononen N, Murakami Y, Nadkarni GN, Nikus K, Pankratz N, Pedersen O, Preuss M, Psaty BM, Raitakari OT, Rich SS, Rodriguez BAT, Rosen JD, Rotter JI, Schubert P, Spracklen CN, Surendran P, Tang H, Tardif JC, Ghanbari M, Völker U, Völzke H, Watkins NA, Weiss S, Cai N, Kundu K, Watt SB, Walter K, Zonderman AB, Cho K, Li Y, Loos RJF, Knight JC, Georges M, Stegle O, Evangelou E, Okada Y, Roberts DJ, Inouye M, Johnson AD, Auer PL, Astle WJ, Reiner AP, Butterworth AS, Ouwehand WH, Lettre G, Sankaran VG, Soranzo N · PubMed 32888494

    ABSTRACT: Summary Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering v

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