CHRNA5 and nicotine: behind the scenes.

Before we load up a Story for our subscribers, the GenEd team reads a lot of literature. A LOT OF LITERATURE. We cull through the peer-reviewed article and reconstruct a historical narrative from the discovery of the variant to the latest interpretation of human phenotypes. At the very end we have two capsule synopses: one for scientists and one for beginners. Here's our "for scientists" summary for the rs16969968 SNP in CHRNA5: "CHRNA5, a well-studied gene in multiple human studies on the genetics of addiction, encodes the alpha 5 subunit of the nicotinic acetylcholine receptor. The rs16969968 SNP changes a phylogenetically conserved aspartate to an asparagine (D398N). The N398 protein has lower maximal responses to nAchR agonists and is strongly associated with increased risk of nicotine addiction. A mouse model of CHRNA5 knockout shows that the alpha5 subunit mediates transmission of aversive stimuli from the habenula to the VTA, decreasing dopamine release at the NAc. Carriers of the rs16969968 rare allele are predicted to have a blunted response to the aversive stimuli associated with drug intake, leading to increased consumption. Human fMRI studies show that the N398 allele is associated with reduced synchronization of a cortex-midbrain circuit involved in addiction behavior." Sounds a lot like most of the "reports" you've probably read for genetics results. Here's our "for beginners" summary for the same SNP in the same gene: "The scientific literature on the rare rs16969968 A allele is complex. In short, this genetic change seems to do two things. First, it lowers the response of the nicotine receptor to the brain’s own stimulating chemicals, lowering dopamine tone. And second, it seems to decrease a different function of the nicotine receptor, that of lowering dopamine when a noxious chemical is taken in. Together, the low basal tone that mediates for a person’s wanting to take something to feel better and the poor response to the noxious effect of certain chemicals creates a greater risk for addiction involving substances that others might find to be not a good drug (tobacco smoke)." Note that the "for beginners" summary has very few abbreviations and focuses closely on what a non-scientist human would care about. We'll make more posts in the future about the process of creating a GenEd Story. If you're interested in learning more, use the "Contact Us" link in the navbar above, or register and upload data to see your free MTHFR report.