At the risk of turning Friday Links into a self-trumpet-blowing occasion, we are happy to report that a number of GNZ contributors (Jeff, Carl and Luke) are authors on a new Crohn’s disease GWAS meta-analysis of 6000 patients that came out in Nature Genetics this week. The study brings the number of Crohn’s associations up to 71, with 30 novel, bringing the proportion of heritability explained up to about 24%; also worth noting that all of the associations from the previous meta-analysis were replicated it this one, showing how the cross-platform independent replication experiments that are now standard have largely obliterated false positives in GWAS. There were also 5 loci that showed evidence of a second, independent signal, which I think is a promising sign of things to come.
The next stage in the Crohn’s association game is a large immune disease collaboration that is currently underway, which will (amongst other things) genotype more than 10k Crohn’s samples on a high-density chip targeting immune-related regions. This will be particularly interesting for fine-mapping and detection of multiple signals at known loci, and I’m expecting a big jump in the heritability explained as this sort of data starts rolling in (see my account of Gonçalo Abecasis’ talk at ASHG to see why I am so optimistic about fine mapping).
A similar story also appeared in Nature Genetics in the form of an association study for age at menarche. What I think is notable about this study is that, in one blow, the genetics of menarche changed from a relatively poorly characterised trait, with a few known loci and less than 1% of heritability accounted for, up to a trait with over 30 variants associated and about 10% of heritability explained.
It is also very cool to see how a definite “gold standard” of GWAS papers has crystallised, with both of the Nature Genetics papers containing extensive replication, functional characterisation using 1000 Genomes data, and pathway analysis (e.g. see the figure to the left, which shows connections between Crohn’s loci). The tools in the GWASers toolbox are growing constantly.
Finally, Happy Thanksgiving to all our American and other turkey-loving readers, and thank you to everyone who gave suggestions about the GNZ readers’ survey, which will be up next week.