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Arriola-Montenegro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Alterations in subcortical brain structure volumes have been found to be associated with several neurodegenerative and psychiatric disorders. At the same time, genome-wide association studies (GWAS) have identified numerous common variants associated with brain structure. In this study, we integrate these findings, aiming to identify proteins, metabolites, or microbes that have a putative causal association with subcortical brain structure volumes via a two-sample Mendelian randomization approach. This method uses genetic variants as instrument variables to identify potentially causal associations between an exposure and an outcome. The exposure data that we analyzed comprised genetic associations for 2,994 plasma proteins, 237 metabolites, and 103 microbial genera. The outcome data included GWAS data for seven subcortical brain structure volumes including accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Eleven proteins and six metabolites were found to have a significant association with subcortical structure volumes. We found causal associations between amygdala volume and granzyme A as well as association between accumbens volume and plasma protease c1 inhibitor. Among metabolites, urate had the strongest association with thalamic volume. No significant associations were detected between the microbial genera and subcortical brain structure volumes. We also observed significant enrichment for biological processes such as proteolysis, regulation of the endoplasmic reticulum apoptotic signaling pathway, and negative regulation of DNA binding. Our findings provide insights to the mechanisms through which brain volumes may be affected in the pathogenesis of neurodevelopmental and psychiatric disorders and point to potential treatment targets for disorders that are associated with subcortical brain structure volumes.

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La aparición de la pandemia causada por el virus SARS-CoV-2 tomó desprevenido al mundo entero. Sin embargo, la reacción ha sido asombrosa. En poco más de un año de la aparición del virus, se cuenta con cientos de vacunas en desarrollo y varias de ellas vienen siendo aplicadas en casi todo el mundo. En este manuscrito revisamos el estado actual del desarrollo de las vacunas, resaltando aquéllas que cuentan con estudios de Fase III (eficacia) o IV (efectividad). Además, revisamos las variantes de interés y de preocupación del virus SARS-CoV-2 detectadas hasta el momento y qué se sabe sobre de la eficacia de las vacunas contra ellas.