| Literature DB >> 29186694 |
Max Lam1, Joey W Trampush2, Jin Yu3, Emma Knowles4, Gail Davies5, David C Liewald6, John M Starr7, Srdjan Djurovic8, Ingrid Melle9, Kjetil Sundet10, Andrea Christoforou11, Ivar Reinvang12, Pamela DeRosse3, Astri J Lundervold13, Vidar M Steen14, Thomas Espeseth10, Katri Räikkönen15, Elisabeth Widen16, Aarno Palotie17, Johan G Eriksson18, Ina Giegling19, Bettina Konte19, Panos Roussos20, Stella Giakoumaki21, Katherine E Burdick22, Antony Payton23, William Ollier24, Ornit Chiba-Falek25, Deborah K Attix26, Anna C Need27, Elizabeth T Cirulli28, Aristotle N Voineskos29, Nikos C Stefanis30, Dimitrios Avramopoulos31, Alex Hatzimanolis30, Dan E Arking32, Nikolaos Smyrnis33, Robert M Bilder34, Nelson A Freimer34, Tyrone D Cannon35, Edythe London34, Russell A Poldrack36, Fred W Sabb37, Eliza Congdon34, Emily Drabant Conley38, Matthew A Scult39, Dwight Dickinson40, Richard E Straub41, Gary Donohoe42, Derek Morris42, Aiden Corvin43, Michael Gill43, Ahmad R Hariri39, Daniel R Weinberger41, Neil Pendleton44, Panos Bitsios45, Dan Rujescu19, Jari Lahti46, Stephanie Le Hellard14, Matthew C Keller47, Ole A Andreassen48, Ian J Deary5, David C Glahn4, Anil K Malhotra49, Todd Lencz50.
Abstract
Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.Entities:
Keywords: GWAS; calcium channel; cerebellum; gene expression; general cognitive ability; neurodevelopment; nootropics; potassium channel; synapse
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Year: 2017 PMID： 29186694 PMCID： PMC5789458 DOI： 10.1016/j.celrep.2017.11.028
Source DB: PubMed Journal: Cell Rep Impact factor: 9.995