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 organization: | Medicum Department of Psychology and Logopedics Institute for Molecular Medicine Finland Elisabeth Ingrid Maria Widen / Principal Investigator Clinicum 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 |
| DOI: | https://doi.org/10.1016/j.celrep.2017.11.028 |
| 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 |
| Peer reviewed: | Yes |
| Rights: | cc_by_nc_nd |
| Usage restriction: | openAccess |
| Self-archived version: | publishedVersion |
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