Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87 740 individuals

Jonathan Coleman, Julien Bryois, Helena A. Gaspar, Philip R Jansen, Jeanne E. Savage, Nathan Skene, Robert Plomin, Ana B. Muñoz-Manchado , Sten Linnarsson, Greg Crawford, Jens Hjerling-Leffler, Patrick F. Sullivan, Danielle Posthuma, Gerome Breen

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Abstract

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78 308) were meta-analyzed with a study comparing 1 247 individuals with mean IQ ~170 to 8 185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.
Original languageEnglish
Pages (from-to)182–197
JournalMolecular Psychiatry
Volume24
Issue number2
Early online date8 Mar 2018
DOIs
Publication statusPublished - 1 Feb 2019

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