thesis

Cognitive epidemiology of ethnic health and the CHRM2 vagal vigour hypothesis

Abstract

Ethnic populations representing areas throughout California were compared regarding cognitive ability, socioeconomic position, and mortality. Cognition and socioeconomic position were inversely correlated with mortality. The single nucleotide polymorphism rs8191992 in the M2 muscarinic receptor gene (CHRM2) was previously linked to IQ and modulation of vagal tone. The CHRM2 vagal vigour hypothesis posits that variation at rs8191992 alters the binding site for a brain-expressed microRNA (hsa-mir-383) thereby changing expression of brain M2 muscarinic receptors to cause pleiotropic effects on cognition and vagus nerve signalling which then affects health via the vagal cholinergic anti-inflammatory pathway. This may help explain ethnic health differences, including the Hispanic Health Paradox, since ethnic differences in rs8191992 allele frequencies correspond to ethnic differences in systemic inflammation and mortality. The rs8191992 A-allele may contribute to the clustering of low IQ and low vagal tone with higher substance abuse, externalizing psychopathology, depression, systemic inflammation, metabolic syndrome, and cardiovascular disease

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