Written by: Stephen Hsu
This is a talk from ESHG 2015, which just happened in Glasgow. The abstract is old; at the talk the author reportedly described something like 70 genome wide significant hits (from an even larger combined sample) which are most likely associated with cognitive ability. This is SSGAC … stay tuned!
Title: C15.1 – Genome-wide association study of 200,000 individuals identifies 18 genome-wide significant loci and provides biological insight into human cognitive function
Keywords: Educational attainment; genome-wide association; cognitive function
Authors: T. Esko1,2,3, on the behalf of Social Science Genetic Association Consortium (SSGAC); 1Estonian Genome Center, University of Tartu, Tartu, Estonia, 2Boston Children’s Hospital, Boston, MA, United States, 3Broad Institute of Harvard and MIT, Cambridge, MA, United States.
Abstract: Educational attainment, measured as years of schooling, is commonly used as a proxy for cognitive function. A recent genome wide association study (GWAS) of educational attainment conducted in a discovery sample of 100,000 individuals identified and replicated three genome-wide significant loci. Here, we report preliminary results based on conducted in 200,000 individuals. We replicate the previous three loci and report 15 novel, genome-wide significant loci for educational attainment. A polygenic score composed of 18 single nucleotide polymorphisms, one from each locus, explains ~0.4% of the variance educational attainment. Applying data-driven computational tools, we find that genes in loci that reach nominal significance (P < 5.0×10-5) strongly enrich for 11 groups of biological pathways (false discovery rates < 0.05) mostly related to the central nervous system, including dendritic spine morphogenesis (P=1.2×10-7), axon guidance (P=5.8×10-6) and synapse organization (P=1.7×10-5), and show enriched expression in various brain areas, including hippocampus, limbic system, cerebral and entorhinal cortex. We also prioritized genes in associated loci and found that several are known to harbor genes related to intellectual disability (SMARCA2, MAPT), obesity (RBFOX3, SLITRK5), and schizophrenia (GRIN2A) among others. By pointing at specific genes, pathways and brain areas, our work provides novel biological insights into several facets of human cognitive function.
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