Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.Peer reviewe

Auditory Afferents:Sound Encoding in the Cochlea

The primary afferent neurons are responsible for the fast and reliable encoding of sound over a wide range of frequencies and intensities. Populations of afferent neurons with heterogenous response properties are required to perform this remarkable incredible feat. This chapter reviews the anatomical, physiological, and genetic mechanisms that define subpopulations of auditory spiral ganglion neurons and afferents that contribute to the encoding of sound. Importantly, these mechanisms also contribute to the susceptibility of the auditory system to acoustic overexposure and aging

Presynaptic physiology of cochlear inner hair cells

Sound based signal transduction happens at ribbon synapses between inner hair cells and spiral ganglion neurons in the cochlea. This chapter reviews the molecular anatomy and physiology of the presynaptic active zones of inner hair cells that are specialized to enable indefatigable glutamate release at high rates and utmost temporal precision