{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:48:32Z","timestamp":1785772112680,"version":"3.56.0"},"reference-count":104,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:00:00Z","timestamp":1686614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIA"},{"name":"NIH\/NIA"},{"DOI":"10.13039\/100011276","name":"University of Washington Alzheimer\u2019s Disease Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alzheimer's disease is characterized by 2 pathological proteins, amyloid beta 42 and tau. The majority of Alzheimer's disease cases in the population are sporadic and late-onset Alzheimer's disease, which exhibits high levels of heritability. While several genetic risk factors for late-onset Alzheimer's disease have been identified and replicated in independent studies, including the ApoE \u03b54 allele, the great majority of the heritability of late-onset Alzheimer's disease remains unexplained, likely due to the aggregate effects of a very large number of genes with small effect size, as well as to biases in sample collection and statistical approaches. Here, we present an unbiased forward genetic screen in Drosophila looking for naturally occurring modifiers of amyloid beta 42- and tau-induced ommatidial degeneration. Our results identify 14 significant SNPs, which map to 12 potential genes in 8 unique genomic regions. Our hits that are significant after genome-wide correction identify genes involved in neuronal development, signal transduction, and organismal development. Looking more broadly at suggestive hits (P &amp;lt; 10\u22125), we see significant enrichment in genes associated with neurogenesis, development, and growth as well as significant enrichment in genes whose orthologs have been identified as significantly or suggestively associated with Alzheimer's disease in human GWAS studies. These latter genes include ones whose orthologs are in close proximity to regions in the human genome that are associated with Alzheimer's disease, but where a causal gene has not been identified. Together, our results illustrate the potential for complementary and convergent evidence provided through multitrait GWAS in Drosophila to supplement and inform human studies, helping to identify the remaining heritability and novel modifiers of complex diseases.<\/jats:p>","DOI":"10.1093\/g3journal\/jkad132","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T15:14:14Z","timestamp":1689174854000},"source":"Crossref","is-referenced-by-count":15,"title":["Using <i>Drosophila<\/i> to identify naturally occurring genetic modifiers of amyloid beta 42- and tau-induced toxicity"],"prefix":"10.1093","volume":"13","author":[{"given":"Ming","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine , Seattle, WA 98195 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Zinkgraf","sequence":"additional","affiliation":[{"name":"Department of Biology, Western Washington University , Bellingham, WA 98225 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Fitzgerald-Cook","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine , Seattle, WA 98195 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine , Seattle, WA 98195 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Putzier","sequence":"additional","affiliation":[{"name":"Department of Biology, Western Washington University , Bellingham, WA 98225 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E L","family":"Promislow","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine , Seattle, WA 98195 , USA"},{"name":"Department of Biology, University of Washington , Seattle, WA 98195 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne M","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology, Western Washington University , Bellingham, WA 98225 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,13]]},"reference":[{"issue":"3","key":"2024022108092668400_jkad132-B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/alz.12328","article-title":"Alzheimer's disease facts and figures","volume":"17","author":"Alzheimer's Association","year":"2021","journal-title":"Alzheimer's Dement"},{"key":"2024022108092668400_jkad132-B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104511","article-title":"The complex genetic architecture of Alzheimer's disease: novel insights and future directions","volume":"90","author":"Andrews","year":"2023","journal-title":"EBioMedicine"},{"issue":"6","key":"2024022108092668400_jkad132-B3","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/0092-8674(91)90262-W","article-title":"Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye","volume":"64","author":"Basler","year":"1991","journal-title":"Cell"},{"issue":"1","key":"2024022108092668400_jkad132-B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Softw"},{"issue":"1","key":"2024022108092668400_jkad132-B5","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B (Methodol)"},{"issue":"1","key":"2024022108092668400_jkad132-B6","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s42003-019-0634-9","article-title":"Multi-trait genome-wide association study identifies new loci associated with optic disc parameters","volume":"2","author":"Bonnemaijer","year":"2019","journal-title":"Commun Biol"},{"issue":"3","key":"2024022108092668400_jkad132-B7","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.ajhg.2016.01.017","article-title":"A statistical approach for testing cross-phenotype effects of rare variants","volume":"98","author":"Broadaway","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"D1","key":"2024022108092668400_jkad132-B8","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"2024022108092668400_jkad132-B9","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","article-title":"Synergy between amyloid-\u03b2 and tau in Alzheimer's disease","volume":"23","author":"Busche","year":"2020","journal-title":"Nat Neurosci"},{"issue":"Suppl 1","key":"2024022108092668400_jkad132-B10","doi-asserted-by":"publisher","first-page":"S277","DOI":"10.3233\/JAD-2012-129011","article-title":"The metal theory of Alzheimer's disease","volume":"33","author":"Bush","year":"2013","journal-title":"J Alzheimers Dis"},{"issue":"12","key":"2024022108092668400_jkad132-B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002822","article-title":"Chapter 11: genome-wide association studies","volume":"8","author":"Bush","year":"2012","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"2024022108092668400_jkad132-B12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/nph.15777","article-title":"Multitrait genome-wide association analysis of Populus trichocarpa identifies key polymorphisms controlling morphological and physiological traits","volume":"223","author":"Chhetri","year":"2019","journal-title":"New Phytol"},{"issue":"5","key":"2024022108092668400_jkad132-B13","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.devcel.2007.10.002","article-title":"Bicaudal-c recruits ccr4-not deadenylase to target mRNAs and regulates oogenesis, cytoskeletal organization, and its own expression","volume":"13","author":"Chicoine","year":"2007","journal-title":"Dev Cell"},{"issue":"6","key":"2024022108092668400_jkad132-B14","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/ng2049","article-title":"Using flyatlas to identify better Drosophila melanogaster models of human disease","volume":"39","author":"Chintapalli","year":"2007","journal-title":"Nat Genet"},{"issue":"4","key":"2024022108092668400_jkad132-B15","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1093\/hmg\/ddv502","article-title":"Candidate genetic modifiers of retinitis pigmentosa identified by exploiting natural variation in Drosophila","volume":"25","author":"Chow","year":"2016","journal-title":"Hum Mol Genet"},{"issue":"7789","key":"2024022108092668400_jkad132-B16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41586-019-1879-7","article-title":"A brief history of human disease genetics","volume":"577","author":"Claussnitzer","year":"2020","journal-title":"Nature"},{"issue":"1","key":"2024022108092668400_jkad132-B17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neuroscience.2004.12.025","article-title":"Intraneuronal abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease","volume":"132","author":"Crowther","year":"2005","journal-title":"Neuroscience"},{"key":"2024022108092668400_jkad132-B18","doi-asserted-by":"publisher","first-page":"516","DOI":"10.3389\/fnins.2020.00516","article-title":"Machine learning representation of loss of eye regularity in a","volume":"14","author":"Diez-Hermano","year":"2020","journal-title":"Front Neurosci"},{"issue":"1","key":"2024022108092668400_jkad132-B19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13024-015-0005-z","article-title":"An automated image analysis method to measure regularity in biological patterns: a case study in a Drosophila neurodegenerative model","volume":"10","author":"Diez-Hermano","year":"2015","journal-title":"Mol Neurodegener"},{"issue":"2","key":"2024022108092668400_jkad132-B20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s00401-016-1662-x","article-title":"Alzheimer's disease: experimental models and reality","volume":"133","author":"Drummond","year":"2017","journal-title":"Acta Neuropathol"},{"issue":"11","key":"2024022108092668400_jkad132-B21","doi-asserted-by":"publisher","first-page":"3323","DOI":"10.1093\/brain\/awq217","article-title":"Blocking adam10 synaptic trafficking generates a model of sporadic Alzheimer's disease","volume":"133","author":"Epis","year":"2010","journal-title":"Brain"},{"issue":"6","key":"2024022108092668400_jkad132-B22","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/S0092-8674(00)81799-7","article-title":"The Drosophila beaten path gene encodes a novel secreted protein that regulates defasciculation at motor axon choice points","volume":"87","author":"Fambrough","year":"1996","journal-title":"Cell"},{"issue":"Pt A","key":"2024022108092668400_jkad132-B23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.expneurol.2015.05.013","article-title":"Modeling the complex pathology of Alzheimer's disease in Drosophila","volume":"274","author":"Fernandez-Funez","year":"2015","journal-title":"Exp Neurol"},{"issue":"6808","key":"2024022108092668400_jkad132-B24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/35040584","article-title":"Identification of genes that modify ataxin-1-induced neurodegeneration","volume":"408","author":"Fernandez-Funez","year":"2000","journal-title":"Nature"},{"issue":"Suppl 3","key":"2024022108092668400_jkad132-B25","doi-asserted-by":"publisher","DOI":"10.1002\/alz.054240","article-title":"Functional exploration of agfg2, a novel player in the pathology of Alzheimer disease","volume":"17","author":"Fernandez","year":"2021","journal-title":"Alzheimers Dement"},{"issue":"3","key":"2024022108092668400_jkad132-B26","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.mcn.2004.03.001","article-title":"A model for studying Alzheimer\u2019s abeta42-induced toxicity in Drosophila melanogaster","volume":"26","author":"Finelli","year":"2004","journal-title":"Mol Cell Neurosci"},{"issue":"3","key":"2024022108092668400_jkad132-B27","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nn.3639","article-title":"Tau promotes neurodegeneration through global chromatin relaxation","volume":"17","author":"Frost","year":"2014","journal-title":"Nat Neurosci"},{"issue":"2","key":"2024022108092668400_jkad132-B28","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1001\/archpsyc.63.2.168","article-title":"Role of genes and environments for explaining Alzheimer disease","volume":"63","author":"Gatz","year":"2006","journal-title":"Arch Gen Psychiatry"},{"issue":"3","key":"2024022108092668400_jkad132-B29","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/nrc3461","article-title":"Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics","volume":"13","author":"Gonzalez","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"2024022108092668400_jkad132-B30","doi-asserted-by":"publisher","author":"Gu","year":"2022","DOI":"10.1016\/j.gpb.2022.04.008"},{"issue":"10","key":"2024022108092668400_jkad132-B31","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-wide association study identifies variants at clu and picalm associated with Alzheimer's disease","volume":"41","author":"Harold","year":"2009","journal-title":"Nat Genet"},{"issue":"1","key":"2024022108092668400_jkad132-B32","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1186\/s12864-020-6739-1","article-title":"The metabolome as a link in the genotype-phenotype map for peroxide resistance in the fruit fly, Drosophila melanogaster","volume":"21","author":"Harrison","year":"2020","journal-title":"BMC Genomics"},{"issue":"2","key":"2024022108092668400_jkad132-B33","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1534\/genetics.113.157800","article-title":"Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin","volume":"196","author":"He","year":"2014","journal-title":"Genetics"},{"issue":"5","key":"2024022108092668400_jkad132-B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064990","article-title":"An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function","volume":"8","author":"Henriksen","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"2024022108092668400_jkad132-B35","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1534\/genetics.116.197228","article-title":"A search for genes mediating the growth-promoting function of tgf\u03b2 in the","volume":"206","author":"Hevia","year":"2017","journal-title":"Genetics"},{"issue":"5","key":"2024022108092668400_jkad132-B36","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/ng.803","article-title":"Common variants at abca7, ms4a6a\/ms4a4e, epha1, cd33 and cd2ap are associated with Alzheimer's disease","volume":"43","author":"Hollingworth","year":"2011","journal-title":"Nat Genet."},{"issue":"1","key":"2024022108092668400_jkad132-B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-12-357","article-title":"An integrative approach to ortholog prediction for disease-focused and other functional studies","volume":"12","author":"Hu","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"2\u20133","key":"2024022108092668400_jkad132-B38","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00429-009-0234-4","article-title":"Transgenic Drosophila models of Alzheimer's disease and tauopathies","volume":"214","author":"Iijima-Ando","year":"2010","journal-title":"Brain Struct Funct"},{"issue":"17","key":"2024022108092668400_jkad132-B39","doi-asserted-by":"publisher","first-page":"6623","DOI":"10.1073\/pnas.0400895101","article-title":"Dissecting the pathological effects of human abeta40 and abeta42 in Drosophila: a potential model for Alzheimer's disease","volume":"101","author":"Iijima","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"2024022108092668400_jkad132-B40","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1093\/gerona\/glv047","article-title":"Longevity gwas using the Drosophila genetic reference panel","volume":"70","author":"Ivanov","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"5","key":"2024022108092668400_jkad132-B41","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1534\/g3.116.027060","article-title":"Quantitative assessment of eye phenotypes for functional genetic studies using Drosophila melanogaster","volume":"6","author":"Iyer","year":"2016","journal-title":"G3 (Bethesda)."},{"issue":"4","key":"2024022108092668400_jkad132-B42","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/S0896-6273(02)00706-7","article-title":"Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila","volume":"34","author":"Jackson","year":"2002","journal-title":"Neuron"},{"issue":"3","key":"2024022108092668400_jkad132-B43","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41588-018-0311-9","article-title":"Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk","volume":"51","author":"Jansen","year":"2019","journal-title":"Nat Genet"},{"issue":"1","key":"2024022108092668400_jkad132-B44","doi-asserted-by":"publisher","DOI":"10.1242\/bio.054627","article-title":"Adenosine triphosphate binding cassette subfamily c member 1 (abcc1) overexpression reduces app processing and increases alpha- versus beta-secretase activity, in vitro","volume":"10","author":"Jepsen","year":"2021","journal-title":"Biol Open"},{"issue":"8","key":"2024022108092668400_jkad132-B45","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1007\/s12035-021-02356-3","article-title":"Proteomic and transcriptomic analyses reveal pathological changes in the entorhinal cortex region that correlate well with dysregulation of ion transport in patients with Alzheimer's disease","volume":"58","author":"Jia","year":"2021","journal-title":"Mol Neurobiol"},{"issue":"8","key":"2024022108092668400_jkad132-B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009713","article-title":"Multitrait GWAS to connect disease variants and biological mechanisms","volume":"17","author":"Julienne","year":"2021","journal-title":"PLoS Genet"},{"issue":"1","key":"2024022108092668400_jkad132-B47","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/s13311-021-01152-0","article-title":"Genomics and functional genomics of Alzheimer's disease","volume":"19","author":"Kamboh","year":"2022","journal-title":"Neurotherapeutics"},{"issue":"4","key":"2024022108092668400_jkad132-B48","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3233\/JAD-2008-15403","article-title":"Modeling tauopathy in the fruit fly Drosophila melanogaster","volume":"15","author":"Khurana","year":"2008","journal-title":"J Alzheimers Dis"},{"issue":"10","key":"2024022108092668400_jkad132-B49","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1172\/JCI57867","article-title":"Cerebral amyloid-\u03b2 proteostasis is regulated by the membrane transport protein abcc1 in mice","volume":"121","author":"Krohn","year":"2011","journal-title":"J Clin Invest"},{"key":"2024022108092668400_jkad132-B50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12748","article-title":"Systematic substrate identification indicates a central role for the metalloprotease adam10 in axon targeting and synapse function","volume":"5","author":"Kuhn","year":"2016","journal-title":"Elife"},{"issue":"3","key":"2024022108092668400_jkad132-B51","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","article-title":"Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates a\u03b2, tau, immunity and lipid processing","volume":"51","author":"Kunkle","year":"2019","journal-title":"Nat Genet"},{"issue":"12","key":"2024022108092668400_jkad132-B52","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat Genet"},{"issue":"47","key":"2024022108092668400_jkad132-B53","doi-asserted-by":"publisher","first-page":"10039","DOI":"10.1021\/bi1016233","article-title":"Preparation and characterization of neurotoxic tau oligomers","volume":"49","author":"Lasagna-Reeves","year":"2010","journal-title":"Biochemistry"},{"issue":"4","key":"2024022108092668400_jkad132-B54","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1534\/genetics.118.301119","article-title":"Genetic modifiers of neurodegeneration in a Drosophila model of Parkinson\u2019s disease","volume":"209","author":"Lavoy","year":"2018","journal-title":"Genetics"},{"issue":"6","key":"2024022108092668400_jkad132-B55","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nrg2563","article-title":"Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants","volume":"10","author":"Lessing","year":"2009","journal-title":"Nat Rev Genet"},{"key":"2024022108092668400_jkad132-B56","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28111","article-title":"Deconstruction of the beaten path-sidestep interaction network provides insights into neuromuscular system development","volume":"6","author":"Li","year":"2017","journal-title":"Elife"},{"issue":"7","key":"2024022108092668400_jkad132-B57","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1021\/acs.accounts.9b00248","article-title":"Metal ions in Alzheimer's disease: a key role or not?","volume":"52","author":"Liu","year":"2019","journal-title":"Acc Chem Res"},{"issue":"1","key":"2024022108092668400_jkad132-B58","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1146\/annurev.genom.7.080505.115758","article-title":"Of flies and man: drosophila as a model for human complex traits","volume":"7","author":"Mackay","year":"2006","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"7384","key":"2024022108092668400_jkad132-B59","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nature10811","article-title":"The Drosophila melanogaster genetic reference panel","volume":"482","author":"Mackay","year":"2012","journal-title":"Nature"},{"issue":"1","key":"2024022108092668400_jkad132-B60","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41398-018-0150-6","article-title":"Gwas on family history of Alzheimer's disease","volume":"8","author":"Marioni","year":"2018","journal-title":"Transl Psychiatry"},{"issue":"2","key":"2024022108092668400_jkad132-B61","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1534\/genetics.115.179457","article-title":"Drosophila as an in vivo model for human neurodegenerative disease","volume":"201","author":"McGurk","year":"2015","journal-title":"Genetics"},{"issue":"4","key":"2024022108092668400_jkad132-B62","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1083\/jcb.200809127","article-title":"Nemo kinase interacts with mad to coordinate synaptic growth at the Drosophila neuromuscular junction","volume":"185","author":"Merino","year":"2009","journal-title":"J Cell Biol"},{"key":"2024022108092668400_jkad132-B63","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2021.772907","article-title":"Comparison of single-trait and multi-trait genome-wide association models and inclusion of correlated traits in the dissection of the genetic architecture of a complex trait in a breeding program","volume":"12","author":"Merrick","year":"2021","journal-title":"Front Plant Sci"},{"issue":"2","key":"2024022108092668400_jkad132-B64","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jalz.2016.09.002","article-title":"Two novel loci, cobl and slc10a2, for Alzheimer's disease in African Americans","volume":"13","author":"Mez","year":"2017","journal-title":"Alzheimers Dement"},{"issue":"5","key":"2024022108092668400_jkad132-B65","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/ng.801","article-title":"Common variants at ms4a4\/ms4a6e, cd2ap, cd33 and epha1 are associated with late-onset Alzheimer's disease","volume":"43","author":"Naj","year":"2011","journal-title":"Nat Genet."},{"issue":"11","key":"2024022108092668400_jkad132-B66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005663","article-title":"Identifying loci contributing to natural variation in xenobiotic resistance in Drosophila","volume":"11","author":"Najarro","year":"2015","journal-title":"PLoS Genet"},{"issue":"5","key":"2024022108092668400_jkad132-B67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034861","article-title":"Multiphen: joint model of multiple phenotypes can increase discovery in GWAS","volume":"7","author":"O\u2019Reilly","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"2024022108092668400_jkad132-B68","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.cell.2013.06.006","article-title":"An extracellular interactome of immunoglobulin and lrr proteins reveals receptor-ligand networks","volume":"154","author":"\u00d6zkan","year":"2013","journal-title":"Cell"},{"issue":"5","key":"2024022108092668400_jkad132-B69","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.mad.2012.02.001","article-title":"Misexpression screen delineates novel genes controlling Drosophila lifespan","volume":"133","author":"Paik","year":"2012","journal-title":"Mech Ageing Dev"},{"issue":"7","key":"2024022108092668400_jkad132-B70","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1093\/bioinformatics\/btq046","article-title":"Ebimage\u2014an r package for image processing with applications to cellular phenotypes","volume":"26","author":"Pau","year":"2010","journal-title":"Bioinformatics"},{"issue":"5","key":"2024022108092668400_jkad132-B71","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/gepi.20589","article-title":"The use of phenome-wide association studies (phewas) for exploration of novel genotype-phenotype relationships and pleiotropy discovery","volume":"35","author":"Pendergrass","year":"2011","journal-title":"Genet Epidemiol"},{"issue":"11","key":"2024022108092668400_jkad132-B72","doi-asserted-by":"publisher","first-page":"3592","DOI":"10.1016\/j.celrep.2019.11.044","article-title":"Amyloid beta and tau cooperate to cause reversible behavioral and transcriptional deficits in a model of Alzheimer's disease","volume":"29","author":"Pickett","year":"2019","journal-title":"Cell Rep"},{"issue":"22","key":"2024022108092668400_jkad132-B73","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.1242\/dev.128.22.4545","article-title":"The beat generation: a multigene family encoding IGSF proteins related to the beat axon guidance molecule in Drosophila","volume":"128","author":"Pipes","year":"2001","journal-title":"Development"},{"issue":"7","key":"2024022108092668400_jkad132-B74","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1007\/s00018-019-03009-4","article-title":"Link between the unfolded protein response and dysregulation of mitochondrial bioenergetics in Alzheimer's disease","volume":"76","author":"Poirier","year":"2019","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"2024022108092668400_jkad132-B75","doi-asserted-by":"publisher","first-page":"3300","DOI":"10.1038\/s41467-019-10936-0","article-title":"Mendelian randomization integrating GWAS and EQTL data reveals genetic determinants of complex and clinical traits","volume":"10","author":"Porcu","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"2024022108092668400_jkad132-B76","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1124\/mol.59.1.83","article-title":"The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines","volume":"59","author":"P\u00f6rzgen","year":"2001","journal-title":"Mol Pharmacol"},{"issue":"3","key":"2024022108092668400_jkad132-B77","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"9","key":"2024022108092668400_jkad132-B78","doi-asserted-by":"publisher","first-page":"3158","DOI":"10.3390\/ijms21093158","article-title":"Utility of animal models to understand human Alzheimer's disease, using the mastermind research approach to avoid unnecessary further sacrifices of animals","volume":"21","author":"Qin","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024022108092668400_jkad132-B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.02.024","article-title":"Assessment of the genetic variance of late-onset Alzheimer's disease","volume":"41","author":"Ridge","year":"2016","journal-title":"Neurobiol Aging"},{"issue":"2","key":"2024022108092668400_jkad132-B80","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/nrg3868","article-title":"Methods of integrating data to uncover genotype-phenotype interactions","volume":"16","author":"Ritchie","year":"2015","journal-title":"Nat Rev Genet"},{"issue":"19","key":"2024022108092668400_jkad132-B81","doi-asserted-by":"publisher","first-page":"4207","DOI":"10.1016\/j.cub.2021.07.017","article-title":"Clockwork orange promotes clock-cycle activation via the putative Drosophila ortholog of clock interacting protein circadian","volume":"31","author":"Rivas","year":"2021","journal-title":"Curr Biol"},{"issue":"32","key":"2024022108092668400_jkad132-B82","doi-asserted-by":"publisher","first-page":"24552","DOI":"10.1074\/jbc.M003476200","article-title":"Cloning and characterization of a Na+-driven anion exchanger (NDAE1). A new bicarbonate transporter","volume":"275","author":"Romero","year":"2000","journal-title":"J Biol Chem"},{"issue":"3","key":"2024022108092668400_jkad132-B83","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/35042080","article-title":"Using Drosophila as a model insect","volume":"1","author":"Schneider","year":"2000","journal-title":"Nat Rev Genet"},{"issue":"1","key":"2024022108092668400_jkad132-B84","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1146\/annurev-genom-083115-022316","article-title":"Thinking about the evolution of complex traits in the era of genome-wide association studies","volume":"20","author":"Sella","year":"2019","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"18","key":"2024022108092668400_jkad132-B85","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1001\/jama.2010.574","article-title":"Genome-wide analysis of genetic loci associated with Alzheimer disease","volume":"303","author":"Seshadri","year":"2010","journal-title":"JAMA"},{"issue":"3","key":"2024022108092668400_jkad132-B86","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1093\/genetics\/165.3.1233","article-title":"Genetic modifiers of tauopathy in Drosophila","volume":"165","author":"Shulman","year":"2003","journal-title":"Genetics"},{"issue":"9","key":"2024022108092668400_jkad132-B87","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1101\/gad.520509","article-title":"Drosophila Motor axons recognize and follow a sidestep-labeled substrate pathway to reach their target fields","volume":"23","author":"Siebert","year":"2009","journal-title":"Genes Dev"},{"issue":"3","key":"2024022108092668400_jkad132-B88","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201910606","article-title":"Novel Alzheimer risk genes determine the microglia response to amyloid-\u03b2 but not to tau pathology","volume":"12","author":"Sierksma","year":"2020","journal-title":"EMBO Mol Med"},{"key":"2024022108092668400_jkad132-B89","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.08493","article-title":"Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy","volume":"4","author":"Todd","year":"2015","journal-title":"Elife"},{"issue":"5","key":"2024022108092668400_jkad132-B90","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/0092-8674(88)90133-X","article-title":"Rough, a Drosophila homeobox gene required in photoreceptors r2 and r5 for inductive interactions in the developing eye","volume":"55","author":"Tomlinson","year":"1988","journal-title":"Cell"},{"issue":"3","key":"2024022108092668400_jkad132-B91","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120236","article-title":"Optomotor-blind negatively regulates Drosophila eye development by blocking JAK\/STAT signaling","volume":"10","author":"Tsai","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"2024022108092668400_jkad132-B92","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00401-015-1525-x","article-title":"Heterotypic seeding of tau fibrillization by pre-aggregated abeta provides potent seeds for prion-like seeding and propagation of tau-pathology in vivo","volume":"131","author":"Vasconcelos","year":"2016","journal-title":"Acta Neuropathol"},{"issue":"11","key":"2024022108092668400_jkad132-B93","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047452","article-title":"Large-scale screen for modifiers of ataxin-3-derived polyglutamine-induced toxicity in Drosophila","volume":"7","author":"VoSSfeldt","year":"2012","journal-title":"PLoS One"},{"issue":"10","key":"2024022108092668400_jkad132-B94","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1093\/bioinformatics\/btm087","article-title":"A new method to measure the semantic similarity of go terms","volume":"23","author":"Wang","year":"2007","journal-title":"Bioinformatics"},{"issue":"5","key":"2024022108092668400_jkad132-B95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v094.i05","article-title":"AssocTests: an R package for genetic association studies","volume":"94","author":"Wang","year":"2020","journal-title":"J Stat Softw"},{"issue":"1","key":"2024022108092668400_jkad132-B96","doi-asserted-by":"publisher","first-page":"5144","DOI":"10.1038\/s41598-021-84534-w","article-title":"Gwas reveal a role for the central nervous system in regulating weight and weight change in response to exercise","volume":"11","author":"Watanabe","year":"2021","journal-title":"Sci Rep"},{"issue":"4","key":"2024022108092668400_jkad132-B97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034745","article-title":"Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster","volume":"7","author":"Weber","year":"2012","journal-title":"PLoS One"},{"issue":"23","key":"2024022108092668400_jkad132-B98","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/j.cub.2003.11.018","article-title":"Two putative acetyltransferases, san and deco, are required for establishing sister chromatid cohesion in Drosophila","volume":"13","author":"Williams","year":"2003","journal-title":"Curr Biol"},{"issue":"5530","key":"2024022108092668400_jkad132-B99","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1126\/science.1062382","article-title":"Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles","volume":"293","author":"Wittmann","year":"2001","journal-title":"Science"},{"issue":"1","key":"2024022108092668400_jkad132-B100","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.cell.2014.09.002","article-title":"A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases","volume":"159","author":"Yamamoto","year":"2014","journal-title":"Cell"},{"issue":"38","key":"2024022108092668400_jkad132-B101","doi-asserted-by":"publisher","first-page":"13670","DOI":"10.1073\/pnas.0504610102","article-title":"Inactivation of Drosophila dj-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase\/akt signaling","volume":"102","author":"Yang","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2024022108092668400_jkad132-B102","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: an r package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"issue":"7","key":"2024022108092668400_jkad132-B103","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1289\/ehp.1510513","article-title":"The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster","volume":"124","author":"Zhou","year":"2016","journal-title":"Environ Health Perspect"},{"issue":"4","key":"2024022108092668400_jkad132-B104","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nmeth.2848","article-title":"Efficient multivariate linear mixed model algorithms for genome-wide association studies","volume":"11","author":"Zhou","year":"2014","journal-title":"Nat Methods"}],"container-title":["G3: Genes, Genomes, Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/g3journal\/advance-article-pdf\/doi\/10.1093\/g3journal\/jkad132\/50892683\/jkad132.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/g3journal\/article-pdf\/13\/9\/jkad132\/56720165\/jkad132.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/g3journal\/article-pdf\/13\/9\/jkad132\/56720165\/jkad132.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T08:10:00Z","timestamp":1708503000000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/g3journal\/article\/doi\/10.1093\/g3journal\/jkad132\/7197291"}},"subtitle":[],"editor":[{"given":"R","family":"Anholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,6,13]]},"references-count":104,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,6,13]]},"published-print":{"date-parts":[[2023,8,30]]}},"URL":"https:\/\/doi.org\/10.1093\/g3journal\/jkad132","relation":{},"ISSN":["2160-1836"],"issn-type":[{"value":"2160-1836","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,6,13]]},"article-number":"jkad132"}}