I do love this figure from the new PR interval paper.
Interestingly 16/25 highlighted genes are in fact the closest gene to the lead SNP.
64%, very similar to eQTLs, pQTLs and metabolite QTLs.
Interestingly 16/25 highlighted genes are in fact the closest gene to the lead SNP.
64%, very similar to eQTLs, pQTLs and metabolite QTLs.
About half the genes in the diagram (the ones with a 7) are also involved in closely related monogenic diseases. This is generally a reliable way to identify a true causal gene.
I looked across all the loci at all genes involved in "rare cardiac diseases"
orpha.net/consor/cgi-bin…
I looked across all the loci at all genes involved in "rare cardiac diseases"
orpha.net/consor/cgi-bin…
First up are genes involved in depolarization and repolarization of the heart. These are all previously known loci, but fall into that nice category of closest gene and also rare disease gene that makes them highly likely to be causal (ok: SCN5A/SCN10A is a special case) 
I also found 2 more genes involved in Ca2+ recycling in the sarcoplasmic reticulum. RYR2 is mentioned in the paper, but TRDN and PLN are not. I found the SNPs by peak-pruning (dist > 1 Mb) the full summary stats and the genes by looking for nearby cardiac monogenic disease genes
TRDN encodes triadin which forms a complex with the RYR2 gene product, the ryanodine receptor.
PLN encodes phospholamban, a regulator of SR Ca2+ release.
en.wikipedia.org/wiki/Phosphola…
PLN encodes phospholamban, a regulator of SR Ca2+ release.
en.wikipedia.org/wiki/Phosphola…
The last batch involves genes involved in heart development.
Did you know the Drosophila homolog of FGFR1 is called "heartless"? I didn't. But it looks like 3 FGF genes and 2 FGFR genes are implicated in this PR GWAS.
en.wikipedia.org/wiki/Heartless…
Did you know the Drosophila homolog of FGFR1 is called "heartless"? I didn't. But it looks like 3 FGF genes and 2 FGFR genes are implicated in this PR GWAS.
en.wikipedia.org/wiki/Heartless…
The transcription factors charged with launching the heart programs include NKX-2, GATA5 and HAND2, all implicated by this GWAS. Two of these have highly relevant monogenic diseases.
pubmed.ncbi.nlm.nih.gov/11994297/
pubmed.ncbi.nlm.nih.gov/11994297/
I would think PR interval counts as a "complex trait."
The fact that the SNPs and genes follow a similar pattern (proximity, related monogenic traits) to metabolites and biomarkers is what gives me some confidence that the lessons learned from metabolite QTLs apply more broadly.
The fact that the SNPs and genes follow a similar pattern (proximity, related monogenic traits) to metabolites and biomarkers is what gives me some confidence that the lessons learned from metabolite QTLs apply more broadly.
