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

• Published in: Molecular psychiatry 2019-02, Vol.24 (2), p.182-197
• Main Authors: Coleman, Jonathan R. I., Bryois, Julien, Gaspar, Héléna A., Jansen, Philip R., Savage, Jeanne E., Skene, Nathan, Plomin, Robert, Muñoz-Manchado, Ana B., Linnarsson, Sten, Crawford, Greg, Hjerling-Leffler, Jens, Sullivan, Patrick F., Posthuma, Danielle, Breen, Gerome
• Format: Article
• Language: English
• Subjects: 45; 45/43; 45/91; 631/208; 631/378; 631/80; Behavioral Sciences; Biological Psychology; Brain; Brain - metabolism; Cognition - physiology; Cohort Studies; Cortex (frontal); Cortex (somatosensory); Data Analysis; Embryos; Female; Frontal Lobe - metabolism; Gene expression; Gene Expression - genetics; Genetic Loci - genetics; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Humans; Immediate Communication; Intelligence; Intelligence - genetics; Intelligence - physiology; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mesencephalon; Meta-analysis; Multifactorial Inheritance - genetics; Nervous system; Neurons; Neurosciences; Pharmacotherapy; Polymorphism, Single Nucleotide - genetics; Psychiatry; Pyramidal cells; Pyramidal Cells - physiology; Systematic review; Temporal Lobe - metabolism; Tissue analysis; Tissues; γ-Aminobutyric acid
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-018-0040-6

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 1247 individuals with mean IQ ~170 to 8185 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.