The role of the circadian clock is becoming apparent in many aspects of human health and disease. Large scale GWAS studies have delivered high numbers of genetic markers for chronotype, which can be used to find links to Mendelian disorders. We used the variants in the 1,000 genomes study to estimate linkage disequilibrium for these chronotype markers. We analysed genes in high linkage disequilibrium with the chronotype markers for enrichment of disease-causing genes, and looked for enrichment of common HPO terms in the wider disease associated genes. We identified that two cardiovascular disorders, cardiomyopathy, and the inherited cardiac arrhythmia Long QT Syndrome, along with the immune system disorder complement component 2 deficiency were significantly enriched MIM diseases. In contrast the most common HPO terms were developmental and neurological terms. This analysis provides a starting point for identifying the circadian contribution to disease outside of the core circadian clock genes, by providing candidate conditions and loci for identifying circadian modifier variants.
A large-scale functional RNAi screen reveals a role for CK2 in the mammalian circadian clock
