Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets

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Lam , M , Trampush , J W , Yu , J , Knowles , E , Davies , G , Liewald , D C , Starr , J M , Djurovic , S , Melle , I , Sundet , K , Christoforou , A , Reinvang , I , DeRosse , P , Lundervold , A J , Steen , V M , Espeseth , T , Raikkonen , K , Widen , E , Palotie , A , Eriksson , J G , Giegling , I , Konte , B , Roussos , P , Giakoumaki , S , Burdick , K E , Payton , A , Ollier , W , Chiba-Falek , O , Attix , D K , Need , A C , Cirulli , E T , Voineskos , A N , Stefanis , N C , Avramopoulos , D , Hatzimanolis , A , Arking , D E , Smyrnis , N , Bilder , R M , Freimer , N A , Cannon , T D , London , E , Poldrack , R A , Sabb , F W , Congdon , E , Conley , E D , Scult , M A , Dickinson , D , Straub , R E , Donohoe , G , Morris , D , Corvin , A , Gill , M , Hariri , A R , Weinberger , D R , Pendleton , N , Bitsios , P , Rujescu , D , Lahti , J , Le Hellard , S , Keller , M C , Andreassen , O A , Deary , I J , Glahn , D C , Malhotra , A K & Lencz , T 2017 , ' Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets ' , Cell Reports , vol. 21 , no. 9 , pp. 2597-2613 . https://doi.org/10.1016/j.celrep.2017.11.028

Title: Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets
Author: Lam, Max; Trampush, Joey W.; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C.; Starr, John M.; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J.; Steen, Vidar M.; Espeseth, Thomas; Raikkonen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Giegling, Ina; Konte, Bettina; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E.; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Attix, Deborah K.; Need, Anna C.; Cirulli, Elizabeth T.; Voineskos, Aristotle N.; Stefanis, Nikos C.; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Arking, Dan E.; Smyrnis, Nikolaos; Bilder, Robert M.; Freimer, Nelson A.; Cannon, Tyrone D.; London, Edythe; Poldrack, Russell A.; Sabb, Fred W.; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A.; Dickinson, Dwight; Straub, Richard E.; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad R.; Weinberger, Daniel R.; Pendleton, Neil; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C.; Andreassen, Ole A.; Deary, Ian J.; Glahn, David C.; Malhotra, Anil K.; Lencz, Todd
Contributor: University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Helsinki Collegium for Advanced Studies
Date: 2017-11-28
Language: eng
Number of pages: 17
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/231511
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.
Subject: GENOME-WIDE ASSOCIATION
SINGLE-NUCLEOTIDE POLYMORPHISMS
LD SCORE REGRESSION
UK BIOBANK N=112151
ADULT HUMAN HEIGHT
EDUCATIONAL-ATTAINMENT
HUMAN INTELLIGENCE
GENE-EXPRESSION
ALZHEIMERS-DISEASE
LOCI
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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