Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
2018
Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3–7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale
genetic associationstudy of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression
quantitative trait locus(eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal
medium spiny neuronsand hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong
genetic correlationswith multiple health-related outcomes, and
Mendelian randomizationanalysis results suggest protective effects of intelligence for Alzheimer’s disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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