Supporting data for "Iterative Hard Thresholding in GWAS: Generalized Linear Models, Prior Weights, and Double Sparsity"
Dataset type: Genomic, Software
Data released on April 08, 2020
Chu BB; Keys KL; German CA; Zhou H; Zhou JJ; Sobel EM; Sinsheimer JS; Lange K (2020): Supporting data for "Iterative Hard Thresholding in GWAS: Generalized Linear Models, Prior Weights, and Double Sparsity" GigaScience Database. https://doi.org/10.5524/100722
Consecutive testing of single nucleotide polymorphisms (SNPs) is usually employed to identify genetic variants associated with complex traits. Ideally one should model all covariates in unison, but most existing analysis methods for genome-wide association studies (GWAS) perform only univariate regression.
We extend and efficiently implement iterative hard thresholding (IHT) for multiple regression, treating all SNPs simultaneously. Our extensions accommodate generalized linear models (GLMs), prior information on genetic variants, and grouping of variants. In our simulations, IHT recovers up to 30% more true predictors than SNP-by-SNP association testing, and exhibits a 2 to 3 orders of magnitude decrease in false positive rates compared to lasso regression. We also test IHT on the UK Biobank hypertension phenotypes and the Northern Finland Birth Cohort of 1966 cardiovascular phenotypes. We find that IHT scales to the large datasets of contemporary human genetics and recovers the plausible genetic variants identified by previous studies.
Our real data analysis and simulation studies suggest that IHT can (a) recover highly correlated predictors, (b) avoid over-fitting, (c) deliver better true positive and false positive rates than either marginal testing or lasso regression, (d) recover unbiased regression coefficients, (e) exploit prior information and group-sparsity and (f) be used with biobank sized data sets. Although these advances are studied for GWAS inference, our extensions are pertinent to other regression problems with large numbers of predictors.
Additional details
Read the peer-reviewed publication(s):
- Chu, B. B., Keys, K. L., German, C. A., Zhou, H., Zhou, J. J., Sobel, E. M., Sinsheimer, J. S., & Lange, K. (2020). Iterative hard thresholding in genome-wide association studies: Generalized linear models, prior weights, and double sparsity. GigaScience, 9(6). https://doi.org/10.1093/gigascience/giaa044 (PubMed:32491161)
Github links:
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Table SettingsFile Name | Description | Sample ID | Data Type | File Format | Size | Release Date | File Attributes | Download |
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Archival copy of the GitHub repository https://github.com/OpenMendel/MendelIHT.jl downloaded 5-Mar-2020. MendelIHT. This project is licensed under the MIT License. Please refer to the GitHub repo for most recent updates. | GitHub archive | archive | 34.58 MB | 2020-03-24 | license: MIT MD5 checksum: a43e1bb8de133548b5b7af9cc6903d92 |
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instructions to users on how to download data from UK Biobank | Text | TEXT | 824 B | 2020-03-24 | MD5 checksum: a277933a2f2c68e044adfb4a374c73cf |
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instructions to users on how to download Stampeed(NFBC1966) data from dbGaP | Text | TEXT | 917 B | 2020-03-24 | MD5 checksum: 5a81b79676e1cd5c59b61c3bad9a50f7 |
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Readme | TEXT | 2.91 kB | 2020-04-08 | MD5 checksum: 33e6d4123b06f01e24e4db7c2717fff0 |
Funding body | Awardee | Award ID | Comments |
---|---|---|---|
National Institute of Health | B Chu | NIH T32-HG002536 | |
B Chu | 2018 Google Summer of Code | ||
National Heart and Lung Institute | K Keys | R01HL135156 | |
Gordon and Betty More Foundation | K Keys | GBMF3834 | |
Alfred P. Sloan Foundation | K Keys | 2013-10-27 | |
National Human Genome Research Institute | K Lange | HG006139 | |
National Human Genome Research Institute | H Zhoa | HG006139 | |
National Institute of General Medical Sciences | K Lange | GM053275 | |
National Institute of General Medical Sciences | H Zhoa | GM053275 | |
National Institute of General Medical Sciences | J Sinsheimer | GM053275 | |
National Human Genome Research Institute | J Sinsheimer | HG009120 | |
National Science Foundation | J Sinsheimer | DMS1264153 | |
Burroughs Wellcome Fund | C German | Inter-school Training Program in Chronic Diseases (BWF-CHIP) |
Date | Action |
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April 8, 2020 | Dataset publish |
April 24, 2020 | Manuscript Link added : 10.1093/gigascience/giaa044 |
October 7, 2022 | Manuscript Link updated : 10.1093/gigascience/giaa044 |