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 GRCh38), gene, endophenotype, or disease.

Currently, ONTIME contains summary statistics for 26428 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. 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: Yueyao Wang, wang.yueyao@wustl.edu

Information Contact: Carlos Cruchaga, cruchagac@wustl.edu

ONTIME was built from the PheWeb code base (version 1.3.16). All genomic positions are on GRCh38. Summary statistics have been drawn from various sources, including the following published studies:

1. Bellenguez, C., Küçükali, F., Jansen, I.E. et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet 54, 412–436 (2022). https://doi.org/10.1038/s41588-022-01024-z

2. Euesden, et al 2023

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. Ali, M., Archer, D.B., Gorijala, P. et al. Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease. acta neuropathol commun 11, 68 (2023). https://doi.org/10.1186/s40478-023-01563-4

5. onggeol Jeffrey Kim, Dan Vitale, Diego Véliz Otani, Michelle Lian, Karl Heilbron, the 23andMe Research Team, Hirotaka Iwaki, Julie Lake, Caroline Warly Solsberg, Hampton Leonard, Mary B. Makarious, Eng-King Tan, Andrew B. Singleton, Sara Bandres-Ciga, Alastair J Noyce, Cornelis Blauwendraat, Mike A. Nalls, Jia Nee Foo, Ignacio Mata. Multi-ancestry genome-wide meta-analysis in Parkinson’s disease. medRxiv 2022.08.04.22278432; doi: https://doi.org/10.1101/2022.08.04.22278432

6. 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

7. 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

8. van Rheenen, W., van der Spek, R.A.A., Bakker, M.K. et al. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat Genet 53, 1636–1648 (2021). https://doi.org/10.1038/s41588-021-00973-1

9. Chia, R., Sabir, M.S., Bandres-Ciga, S. et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet 53, 294–303 (2021). https://doi.org/10.1038/s41588-021-00785-3

10. International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460):eaav7188. doi: 10.1126/science.aav7188. PMID: 31604244; PMCID: PMC7241648.

11. Carlos Cruchaga, Dan Western, Jigyasha Timsina et al. Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and informs causal proteins for Alzheimer’s disease, 09 June 2023, PREPRINT (Version 1) available at Research Square. [https://doi.org/10.21203/rs.3.rs-2814616/v1]

12. Ciyang Wang, Dan Western, Chengran Yang et al. Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness, 09 June 2023, PREPRINT (Version 1) available at Research Square. [https://doi.org/10.21203/rs.3.rs-2923409/v1]

This site was built with PheWeb version 1.3.16.

NeuroGenomics and Informatics

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