The Online Neurodegenerative Trait Integrative Multi-Omics Explorer (ONTIME) is a web-based catalogue of genome wide association studies dedicated to quantitative neurodegenerative disease endophenotypes. Users can search for associations to common and low-frequency variants by variant (by either rsID or chromosome:position on GRCh37), gene, endophenotype, or therapeutic category.

Currently, ONTIME contains summary statistics for 2926 quantitative endophenotypes. Only associations for autosomes are displayed. Alleles (effect and non-effect) for each variant across all datasets have been aligned against those in dbSNP’s Human Build 150. Therefore, variants across all Manhattan plots display a standardized direction of effect. Summary statistics have also been filtered to remove variants without data for beta or p-value fields (eg, beta = NA).

Developer Contact: Brett Eiffert - beiffert@wustl.edu

Information Contact: Oscar Harari - harario@wustl.edu

ONTIME was built from the PheWeb code base. All genomic positions are on GRCh37. Summary statistics have been drawn from various sources, including the following published studies:

1. Li Z, Farias FG, Dube U, Del-Aguila JL, Mihindukulasuriya KA, Fernandez MV, Ibanez L, Budde JP, Wang F, Lake AM, Deming Y, Perez J, Yang C, Bradley J, Davenport R, Bergmann K, Benitez BA, Dougherty JD, Harari O, Cruchaga C. The TMEM106B rs1990621 protective variant is also associated with increased neuronal proportion. bioRxiv 583286; 2019. doi:https://doi.org/10.1101/583286
2. Yan Q, Nho K, Del-Aguila JL, Wang X, Risacher SL, Fan KH, Snitz BE, Aizenstein HJ, Mathis CA, Lopez OL, Demirci FY, Feingold E, Klunk WE, Saykin AJ; Alzheimer’s Disease Neuroimaging Initiative (ADNI), Cruchaga C, Kamboh MI. Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging. Mol Psychiatry. 2018; Oct 25. doi: 10.1038/s41380-018-0246-7 PMCID: PMC6219464
3. Del-Aguila JL, Fernández MV, Schindler S, Ibanez L, Deming Y, Ma S, Saef B, Black K, Budde J, Norton J, Chasse R; Alzheimer’s Disease Neuroimaging Initiative (ADNI), Harari O, Goate A, Xiong C, Morris JC, Cruchaga C. Assessment of the Genetic Architecture of Alzheimer’s Disease Risk in Rate of Memory Decline. J Alzheimers Dis. 2018; 62(2):745-756. PMCID: PMC5989565
4. Huang KL, Marcora E, Pimenova AA, DiNarzo AF, Kapoor M, Jin SC, Harari O, Bertelsen S, Fairfax BP, Czajkowski J, Kauwe JSK, Cruchaga C, Hao K, Goate AM. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat Neuroscience 2017. 20(8):1052-1061. PMCID: PMC5759334
5. Deming Y, Li Z, Kapoor M, Harari O, Del-Aguila JL, Black K, Carrell D, Cai Y, Fernandez MV, Budde J, Ma S, Saef B, Howells B, Huang KL, Bertelsen S, Fagan AM, Holtzman DM, Morris JC, Kauwe JS, Goate AM, Cruchaga C. Genome-wide association study identifies four novel loci associated with Alzheimer’s endophenotypes and disease modifiers. Acta Neuropathol. 2017; 133(5):839-856. PMCID: PMC5613285
6. Deming Y, Filipello F, Cignarella F, Cantoni C, Hsu S, Mikesell R, Li Z, Del-Aguila JL, Dube U, Farias FG, Bradley J, Benitez B, Budde J, Ibanez L, Fernandez MV, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Dominantly Inherited Alzheimer Network (DIAN), Blennow K, Zetterberg H, Heslegrave A, Johansson PM, Svensson J, Nellgård B, Lleo A, Alcolea D, Clarimon J, Rami L, Molinuevo JL, Suarez-Calvet M, Morenas-Rodríguez E, Kleinberger G, Ewers M, Harari O, Haass C, Brett TJ, Karch CM, Piccio L, Cruchaga C. The MS4A gene cluster is a key regulator of soluble TREM2 and Alzheimer disease risk. bioRxiv 352179; 2018. doi: https://doi.org/10.1101/352179
7. Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC et al (2019) Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet 2019; 51(3):414430. doi: 10.1038/s41588-019-0358-2
8. Kauwe JS, Bailey MH, Ridge PG, Perry R, Wadsworth ME, Hoyt KL, Staley LA, Karch CM, Harari O, Cruchaga C, Ainscough BJ, Bales K, Pickering EH, Bertelsen S; the Alzheimer’s Disease Neuroimaging Initiative, Fagan AM, Holtzman DM, Morris JC, Goate AM. Genome-Wide Association Study of CSF Levels of 59 Alzheimer’s Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. PloS Genet 2014; 10(10):e1004758. PMCID: PMC4207667
9. Ferrari R, Hernandez DG, Nalls MA, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol. 2014; 13(7):686‐699. doi:10.1016/S1474-4422(14)70065-1
10. Nalls MA, Blauwendraat C, Vallerga CL, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019; 18(12):1091‐1102. doi:10.1016/S1474-4422(19)30320-5

NeuroGenomics and Informatics


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