Analysis of sequencing data of 320k individuals (75k cases and 245k controls) shows heterozygous carriers of cystic fibrosis mutations are protected from inflammatory bowel disease. The protection mechanism could be due to an altered gut mucosal barrier that resists penetration by bacterial or other toxins. Prior animal studies have indeed shown that heterozygous state of cystic fibrosis mutation protects against cholera and typhoid bacterial toxins. It's amazing to see validation using human genetics with IBD as outcome. This was one of the ASHG abstracts this year that stood out for me. Nice to see it in preprint. Yu et al. medRxiv (from International IBD consortium) medrxiv.org/content/10.1101/…

A Sunday read for you. A new blog post on a discovery of a noncoding mutation that causes a Mendelian cardiac arrhythmia through a fascinating mechanism: de novo creation of cardiomyocyte-specific enhancer. This adds to the list of my favorite noncoding discoveries that I've highlighted over the past couple of years. Two take homes for me are - when searching noncoding disease variants, we tend to look at regions previously known to play a regulatory role (promoters, enhancers etc.). This work reminds us of the possibility that disease variants might be creating a new regulatory element themselves. - when searching for causal genes, we tend to look at only those that are expressed in the disease-relevant tissues. This work reminds us that causal genes can be the ones that are not expressed in disease-relevant tissues. Sometimes the answers come from places where we least expect to find. Congratulations to the authors on this beautiful work! gwasstories.com/p/de-novo-en…