Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Davies, G. et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications, 9, 2098. (doi: 10.1038/s41467-018-04362-x) (PMID:29844566) (PMCID:PMC5974083)

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10 ) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

• Item Type: Articles
• Additional Information: This research was conducted in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, funded by the Biotechnology and Biological Sciences Research Council and Medical Research Council (MR/K026992/1). This research was conducted using the UK Biobank Resource (Application Nos. 10279 and 4844). The Neurology Working Group within the Cohorts for Heart and Aging Research in Genomic Epidemiology is partly supported by grants from the National Institute on Aging (R01 AG033193, U01 AG049505 and U01 AG052409). Cohort-specific acknowledgements are in Supplementary Note 3.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian
• Authors: Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C.M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L.K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D. E., Hayward, C., Hofer, E., Ikram, M. A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K. A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C. A., Sargurupremraj, M., Scholz, M., Smith, J. A., Smith, A. V., Terzikhan, N., Thalamuthu, A., Trompet, S., van der Lee, S. J., Ware, E. B., Windham, B. G., Wright, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O. A., Armstrong, N. J., Assareh, A. A., Attia, J. R., Attix, D., Avramopoulos, D., Bennett, D. A., Böhmer, A. C., Boyle, P. A., Brodaty, H., Campbell, H., Cannon, T. D., Cirulli, E. T., Congdon, E., Conley, E. D., Corley, J., Cox, S. R., Dale, A. M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J. G., Evangelou, E., Faul, J. D., Ford, I., Freimer, N. A., Gao, H., Giegling, I., Gillespie, N. A., Gordon, S. D., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Hartmann, A. M., Hatzimanolis, A., Heiss, G., Holliday, E. G., Joshi, P. K., Kähönen, M., Kardia, S. L.R., Karlsson, I., Kleineidam, L., Knopman, D. S., Kochan, N. A., Konte, B., Kwok, J. B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S.-C., Liu, T., Koini, M., London, E., Longstreth, W. T., Lopez, O. L., Loukola, A., Luck, T., Lundervold, A. J., Lundquist, A., Lyytikäinen, L.-P., Martin, N. G., Montgomery, G. W., Murray, A. D., Need, A. C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R. A., Psaty, B. M., Reppermund, S., Riedel-Heller, S. G., Rose, R. J., Rotter, J. I., Roussos, P., Rovio, S. P., Saba, Y., Sabb, F. W., Sachdev, P. S., Satizabal, C. L., Schmid, M., Scott, R. J., Scult, M. A., Simino, J., Slagboom, P. E., Smyrnis, N., Soumaré, A., Stefanis, N. C., Stott, D. J., Straub, R. E., Sundet, K., Taylor, A. M., Taylor, K. D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A. N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K. H., Widen, E., Yang, Q., Zhao, W., Adams, H. H.H., Arking, D. E., Bilder, R. M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P. L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A. L., Gill, M., Glahn, D. C., Hägg, S., Hansell, N. K., Hariri, A. R., Ikram, M. K., Jukema, J. W., Vuoksimaa, E., Keller, M. C., Kremen, W. S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N. L., Pendleton, N., Porteous, D. J., Räikkönen, K., Raitakari, O. T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P. W., Schofield, P. R., Starr, J. M., Steen, V. M., Trollor, J. N., Turner, S. T., Van Duijn, C. M., Villringer, A., Weinberger, D. R., Weir, D. R., Wilson, J. F., Malhotra, A., McIntosh, A. M., Gale, C. R., Seshadri, S., Mosley, T. H., Bressler, J., Lencz, T., and Deary, I. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Nature Communications 9:2098
• Publisher Policy: Reproduced under a Creative Commons License