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Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.
Tuesday,2018-05-01 17:52 America/Los_Angeles — ecterry
| Title | Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Lam, M, Trampush, JW, Yu, J, Knowles, E, Davies, G, Liewald, DC, Starr, JM, Djurovic, S, Melle, I, Sundet, K, Christoforou, A, Reinvang, I, DeRosse, P, Lundervold, AJ, Steen, VM, Espeseth, T, Räikkönen, K, Widen, E, Palotie, A, Eriksson, JG, Giegling, I, Konte, B, Roussos, P, Giakoumaki, S, Burdick, KE, Payton, A, Ollier, W, Chiba-Falek, O, Attix, DK, Need, AC, Cirulli, ET, Voineskos, AN, Stefanis, NC, Avramopoulos, D, Hatzimanolis, A, Arking, DE, Smyrnis, N, Bilder, RM, Freimer, NA, Cannon, TD, London, E, Poldrack, RA, Sabb, FW, Congdon, E, Conley, EDrabant, Scult, MA, Dickinson, D, Straub, RE, Donohoe, G, Morris, D, Corvin, A, Gill, M, Hariri, AR, Weinberger, DR, Pendleton, N, Bitsios, P, Rujescu, D, Lahti, J, Le Hellard, S, Keller, MC, Andreassen, OA, Deary, IJ, Glahn, DC, Malhotra, AK, Lencz, T |
| Journal | Cell Rep |
| Volume | 21 |
| Issue | 9 |
| Pagination | 2597-2613 |
| Date Published | 2017 Nov 28 |
| ISSN | 2211-1247 |
| Abstract | <p>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.</p> |
| DOI | 10.1016/j.celrep.2017.11.028 |
| Alternate Journal | Cell Rep |
| PubMed ID | 29186694 |
| PubMed Central ID | PMC5789458 |
| Grant List | UL1 RR033176 / RR / NCRR NIH HHS / United States R01 AG049789 / AG / NIA NIH HHS / United States R01 MH079800 / MH / NIMH NIH HHS / United States R01 AA009367 / AA / NIAAA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268201500001C / HL / NHLBI NIH HHS / United States K01 MH098126 / MH / NIMH NIH HHS / United States R01 DA033369 / DA / NIDA NIH HHS / United States K01 MH085812 / MH / NIMH NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R01 AA011886 / AA / NIAAA NIH HHS / United States PL1 MH083271 / MH / NIMH NIH HHS / United States R01 MH085018 / MH / NIMH NIH HHS / United States RL1 MH083269 / MH / NIMH NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States UL1 DE019580 / DE / NIDCR NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States U01 DA024417 / DA / NIDA NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States RC2 MH089924 / MH / NIMH NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States PL1 NS062410 / NS / NINDS NIH HHS / United States HHSN268201500001I / HL / NHLBI NIH HHS / United States P50 MH080173 / MH / NIMH NIH HHS / United States R01 MH066140 / MH / NIMH NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States U01 AG023746 / AG / NIA NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States K23 MH077807 / MH / NIMH NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 MH092515 / MH / NIMH NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R37 DA005147 / DA / NIDA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States RL1 DA024853 / DA / NIDA NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States RC2 MH089983 / MH / NIMH NIH HHS / United States R01 MH080912 / MH / NIMH NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States R01 DA013240 / DA / NIDA NIH HHS / United States |
ePub date:
17/09