This effort will not only help in the identification of functional variants, it will also provide valuable insight into the connection between functional variants and the pathogenesis of autoimmune diseases in the context of different organs and tissues.
This is an intergenic SNP that lies between PAWR and PPP1R12A and it may be in linkage disequilibrium with functional variants in either gene, although PAWR as a tumor suppressor is a more likely candidate.
To identify the actual functional variants in the ESR1 gene that affect height will require re-sequencing of the genes to identify possible rare variants, and functional studies on the molecular level, as well as very large population-based studies on the interactions between genes and with factors from the environment.
In the first GWAS of menstrual cycle length, we found a strong association between an FSH lowering, likely functional, variant in the FSHB promoter and longer cycles (Hoogendoorn et al., 2003; Grigorova et al., 2008, 2010; Tuttelmann et al., 2012; Benson et al., 2013; La Marca et al., 2013; Simoni and Casarini, 2014; Ruth et al., 2015).
Assuming the same functional variant in the Swedish and the Finnish samples, the two samples would assist in narrowing the interval of that functional variant (Fig. 2C).
Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene.
The actual functional variant in the ADAMTS9 region is not known, and the rs4607103 SNP may not be the functional variant in this region.
Several recent sequencing studies provide additional evidence for this relationship between predicted functional variants and phenotype [30], [33], [34], [39].
Instead of learning to discriminate between known functional variants and controls, CADD uses a training set composed of variants that have become fixed in the human lineage, and which therefore presumably represent tolerable variation, and simulated variants that are not observed in human populations.
