Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

American Journal of Human Genetics
Max LamTodd Lencz

Abstract

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophr...Continue Reading

Citations

Apr 28, 2020·Annual Review of Genomics and Human Genetics·Piero PeruccaSamuel F Berkovic
Oct 9, 2020·International Journal of Epidemiology·Andrew McMartin, Dalton Conley
Jan 30, 2021·Scientific Reports·Nadezhda M BelonogovaTatiana I Axenovich
Feb 4, 2021·Molecular Psychiatry·Ian J DearyW David Hill
May 27, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Max LamTodd Lencz
Jun 24, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Chiara FabbriAlessandro Serretti
Jun 29, 2021·Frontiers in Human Neuroscience·Hayley S MountfordDianne F Newbury
Jul 24, 2021·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Duncan E AstleSusan E Gathercole
Oct 17, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Anastasia LevchenkoSvetlana A Ivanova
Dec 18, 2020·Chemical Research in Toxicology·Jianhui ChenGuixia Liu
Nov 6, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Miruna Carmen BarbuHeather Whalley

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