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

Show full item record



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 .

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 organization: Medicum
Department of Psychology and Logopedics
Institute for Molecular Medicine Finland
Elisabeth Ingrid Maria Widen / Principal Investigator
Aarno Palotie / Principal Investigator
Department of Medical and Clinical Genetics
Johan Eriksson / Principal Investigator
Department of General Practice and Primary Health Care
Helsinki Collegium for Advanced Studies
Developmental Psychology Research Group
Genomics of Neurological and Neuropsychiatric Disorders
Genomic Discoveries and Clinical Translation
Date: 2017-11-28
Language: eng
Number of pages: 17
Belongs to series: Cell Reports
ISSN: 2211-1247
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.
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
1_s2.0_S2211124717316480_main.pdf 4.275Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record