Genetic variants associated with alcohol dependence co-ordinate regulation of ADH genes in gastrointestinal and adipose tissues

This repository contains scripts, data, results, figures and reproducibility report for "Genetic variants associated with alcohol dependence co-ordinate regulation of ADH genes in gastrointestinal and adipose tissues" study published in Scientific Reports. In this study, we integrate data from multiple sources (i.e. GWAS catalog, Hi-C, GTEx, HaploReg data) to analyze 73 AD associated SNPs and identify 34 expression quantitative loci (eQTL) with potential regulatory roles that impact alcohol dependence. We report that 42% of the 285 significant tissue-specific regulatory interactions we identify were associated with four genes encoding Alcohol Dehydrogenase - ADH1A, ADH1B, ADH1C and ADH4. Identified eQTLs produced a coordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues.

Python (version 2.7.15), R (version 3.5.2) and RStudio (version 1.1.463) were used for data processing, analysis and visualisation.

1. Cell type- and tissue-specific Hi-C data is available on GEO database (accessions: GSE63525, GSE35156, GSE43070, GSE77565, GSE105194, GSE105513, GSE105544, GSE52457, GSE105914, GSE105957, GSE87112).
2. RNA-seq and genotyping data (GTEx v7) are available via dbGaP access (accession: phs000424.v7.p2).
3. Human genome build hg19 release 75 (GRCh37) (“Homo_sapiens.GRCh37.75.dna.primary_assembly.fa.gz”) was downloaded from ftp://ftp.ensembl.org/pub/release-75/fasta/homo_sapiens/dna/.
4. SNP genomic positions were obtained from ftp://ftp.ncbi.nih.gov/snp/organisms/human_9606_b151_GRCh37p13/.
5. Gene annotation for GENCODE v19 (“gencode.v19.transcripts.patched_contigs.gtf”) was downloaded from https://storage.googleapis.com/gtex_analysis_v7/reference/.
6. SNPs associated with alcohol dependence were downloaded from the GWAS Catalog on 07/12/2018.
7. Promoter-enhancer histone marks and affected regulatory motifs were obtained from the HaploReg (version 4.1).

 

Tissue-specific effects of eQTLs for ADH1A, ADH1B, ADH1C and ADH4 mapped to the human body. Red text denotes the SNP upregulates the eGene, whereas blue text denotes downregulation.