Genetic Association of Phosphodiesterases With Human Cognitive Performance

Frontiers in Molecular Neuroscience
Mark E Gurney

Abstract

Recent, large-scale, genome-wide association studies (GWAS) provide a first view of the genetic fine structure of cognitive performance in healthy individuals. These studies have pooled data from up to 1.1 million subjects based on simple measures of cognitive performance including educational attainment, self-reported math ability, highest math class taken, and pooled, normalized scores from cognitive tests. These studies now allow the genome-wide interrogation of genes and pathways for their potential impact on human cognitive performance. The phosphodiesterase (PDE) enzymes regulate key cyclic nucleotide signaling pathways. Many are expressed in the brain and have been the targets of CNS drug discovery. Genetic variation in PDE1C, PDE4B and PDE4D associates with multiple measures of human cognitive function. The large size of the human PDE4B and PDE4D genes allows genetic fine structure mapping to transcripts encoding dimeric (long) forms of the enzymes. Upstream and downstream effectors of the cAMP pathway modulated by PDE4D [adenylate cyclase 1 (ADCY1), ADCY8, PRKAR1A, CREB1, or CREBBP] did not show genetic association with cognitive performance, however, genetic association was seen with brain derived neurotrophic factor ...Continue Reading

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Citations

Sep 7, 2019·The Journal of Pharmacology and Experimental Therapeutics·Su-Ying CuiJames M O'Donnell
Aug 10, 2019·Frontiers in Immunology·Melissa SchepersTim Vanmierlo
Jan 9, 2021·Molecular Psychiatry·Sébastien Delhaye, Barbara Bardoni
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Oct 12, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Liwei MeiHao Yu

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