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Longitudinal Blood DNA Methylation Changes During Weight-Loss Intervention and Dementia Progression Risk

David Lukacsovich, Juan I. Young, Lissette Gomez, Wei Zhang1, Brian W. Kunkle, X. Steven Chen, Eden R. Martin, Lily Wang

Description

This GitHub repository includes scripts used for the analyses in the above manuscript and the resulting summary statistics.

Weight loss improves metabolic health, but the DNA methylation (DNAm) changes induced by the lifestyle intervention and their relevance to dementia outcomes remain unclear. We studied longitudinal blood DNAm changes during an 18-month weight-loss intervention in the CENTRAL clinical trial and evaluated their relevance to dementia progression in an external cohort.

1. Pre-processing DNA methylation data

File Link
code/preprocessing/01a_get_phenotype.Rmd Link to the script
code/preprocessing/01b_get_data.Rmd Link to the script
code/preprocessing/01c_filter_probes.Rmd Link to the script
code/preprocessing/01d_impute_autosomal.Rmd Link to the script
code/preprocessing/01e_normalize_autosomal.Rmd Link to the script
code/preprocessing/01f_batch.Rmd Link to the script
code/preprocessing/01g_pca.Rmd Link to the script

2. Identify diet-related CpGs

File Link
code/preprocessing/02a_time_correlation.Rmd Link to the script
code/preprocessing/02b_bacon_correct.Rmd Link to the script
code/preprocessing/02c_pathway_analysis.Rmd Link to the script
code/preprocessing/02d_compare_correlation.Rmd Link to the script

3. Identify diet-related DMRs and do integrative analysis (eQTm, brain-blood DNAm correlations)

File Link
code/preprocessing/03a_get_sample_statistics.Rmd Link to the script
code/preprocessing/03b_prepare_combp.Rmd Link to the script
code/preprocessing/03c_summarize_combp.Rmd Link to the script
code/preprocessing/03d_eQTM_association.Rmd Link to the script
code/preprocessing/03e_brain_blood_correlation.Rmd Link to the script
code/preprocessing/03f_miami_ad_comparison.Rmd Link to the script
code/preprocessing/03g_ewas_association.Rmd Link to the script

4. Miami-plot to Summarize Results

File Link
code/markdown/04a_miami_plot.Rmd Link to the script

5. Pre-process ADNI DNA methylation data for comparison

File Link
code/ADNI_repeated_measures/01a_get_phenotype.Rmd Link to the script
code/ADNI_repeated_measures/01b_get_data.Rmd Link to the script
code/ADNI_repeated_measures/01c_filter_probes.Rmd Link to the script
code/ADNI_repeated_measures/01d_impute_autosomal.Rmd Link to the script
code/ADNI_repeated_measures/01e_normalize_autosomal.Rmd Link to the script
code/ADNI_repeated_measures/01f_batch.Rmd Link to the script
code/ADNI_repeated_measures/01g_pca.Rmd Link to the script
code/ADNI_repeated_measures/01h_get_sample_statistics.Rmd Link to the script

6. Methylation-based Reserve Scores

File Link
code/MRS_model/01a_correlation_score_diet_only.Rmd Link to the script
code/MRS_model/01b_correlation_score_diet_plus_pa.Rmd Link to the script

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Impact of diet and physical activity on DNA methylation

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