Follow up to GWAS:
Sequence regions near most significant SNPs, sequence all local genes
Transcriptome studies using lymphoblastoid cell lines - PLoS Genetics 2010
SNPs with highest eQTLs are enriched for WTCCC Crohn's susceptibility loci
+other loci too. Pattern different in CAD, Hypertension, T2D.
Enrichment of locally acting eQTLs versus distantly acting eQTLs.
T2D had most dramatic enrichment in a late bin-- transcriptome studies using adipose and muscle tissue.
Most QTLs are distant regulators of gene expression.
Took top 1K SNPs in WTCCC T2D studies. Vast majority enriched for eQTLs acting distantly.
Cancer mostly local regulators.
T1D more local than distant.
Distant regulators quite often on different chromosomes.
Will different phenotypes have different architecture WRT distant vs. local regulators?
Does tissue specificitiy play a role?
Has implications for how we think about sequencing studies.