psychimmgen2021

Code to accompany paper: Lynall et al. Nature Communications 2022 Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells

Version of code used to generate paper is archived at

Datasets generated

Partitioned LD scores for active regulatory regions for ROADMAP epigenomics tissues are available on Zenodo

Scripts

ROADMAP ANALYSIS

• psychimmgenA01 Get IDEAS trackhubs and name roadmap samples
• psychimmgenA02 Convert IDEAS tracks to bed file of ranges for the active states
• psychimmgenA03 Make ldcts, annotations, then partition LD scores for the active elements
• psychimmgenA04 Make nongenic enhancers bed files
• psychimmgenA05 Make promoter and genicenhancer bed files
• psychimmgenA06 Make thin annots from the separate annotations bed files (promoters and enhancers) and make ldcts regression files
• psychimmgenA07 Submission script for partitioning of LD scores
• psychimmgenA08 Process cross-disorder summary statistics (SS), then do normal and conditional s-LDSC analysis
• psychimmgenA09 Process MDD SSs and do s-LDSC
• psychimmgenA10 Process RA SSs and do s-LDSC
• psychimmgenA11 Process SZS SSs and do s-LDSC
• psychimmgenA12 Process BMI SSs and do s-LDSC
• psychimmgenA13 Process ASD SSs and do s-LDSC
• psychimmgenA14 Process Alzheimer's SSs and do s-LDSC
• psychimmgenA15 Process ADHD SSs and do s-LDSC
• psychimmgenA16 Process bipolar disorder SSs and do s-LDSC
• psychimmgenA17 Integrate s-LDSC results across disorders
• psychimmgenA18 s-LDSC for component annotations (separate promoters and enhancers)
• psychimmgenA19 View promoter/enhancer s-LDSC results from psychimmgenA18
• psychimmgenA20 Test correlations between s-LDSC z-scores and heritability z-scores

Summary statistic harmonization and lead loci identification detection

• psychimmgenB01 Convert sumstats to format required by harmonization pipeline and call harmonization pipeline for crossdisorder risk
• psychimmgenB02 Repeat of psychimmgenB01 processing for disorder-specific risks
• psychimmgenB03 Convert harmonized tsv to parquet format
• psychimmgenB04 Generate r2 linkage disequilibrium for 1KG EUR hg38 then filter summary stats on 1KG SNPs
• psychimmgenB05 Use Apache Spark to do distance-based clumping for the 1KG filtered SNPs

CHEERS analysis of BLUEPRINT immune cell subsets and Soskic immune stimulation datasets

• psychimmgenB06 Generate LD blocks and compute CHEERS enrichment for BLUEPRINT and Soskic datasets
• psychimmgenB07 Reformat results to obtain top loci
• psychimmgenB08 Process and visualise BLUEPRINT results
• psychimmgenB09 Process and visualise Soskic dataset results
• psychimmgenB10 Z-test to compare results for stimulated vs. unstimulated immune cells
• psychimmgenB11 Find nearest genes and perform overrepresentation (pathway) analysis

Response to reviewers

• psychimmgen_revisions01 Identify and visualise Soskic MDD-SZS discordant variant-peak overlaps
• psychimmgen_revisions02 Identify and visualise Blueprint MDD-SZS discordant variant-peak overlaps
• psychimmgen_revisions03 Blueprint vs Soskic – is replication driven by overlap of regulatory elements?
• psychimmgen_revisions04 Characteristics of Soskic and Blueprint MDD-SZS discordant peaks