Rxivist logo

GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence

By Jeanne E Savage, Philip R Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A de Leeuw, Mats Nagel, Swapnil Awasthi, Peter B Barr, Jonathan R. I. Coleman, Katrina L. Grasby, Anke R Hammerschlag, J. Kaminski, Robert Karlsson, Eva Krapohl, Max Lam, Marianne Nygaard, Chandra A. Reynolds, Joey W. Trampush, Hannah Young, Delilah Zabaneh, Sara Hägg, Narelle K. Hansell, Ida K. Karlsson, Sten Linnarsson, Grant W. Montgomery, Ana B Muñoz-Manchado, Erin B. Quinlan, Gunter Schumann, N. G. Skene, Bradley T. Webb, Tonya White, Dan E. Arking, Deborah K. Attix, Dimitrios G. Avramopoulos, Robert M. Bilder, Panos Bitsios, Katherine E. Burdick, Tyrone D. Cannon, Ornit Chiba-Falek, Andrea Christoforou, Elizabeth T. Cirulli, Eliza Congdon, Aiden Corvin, Gail Davies, Ian Deary, Pamela DeRosse, Dwight Dickinson, Srdjan Djurovic, Gary Donohoe, Emily Drabant Conley, Johan G. Eriksson, Thomas Espeseth, Nelson A. Freimer, Stella Giakoumaki, Ina Giegling, Michael Gill, David C Glahn, Ahmad R Hariri, Alex Hatzimanolis, Matthew C. Keller, Emma Knowles, Bettina Konte, Jari Lahti, Stephanie Le Hellard, Todd Lencz, David C Liewald, Edythe London, Astri J. Lundervold, Anil K. Malhotra, Ingrid Melle, Derek Morris, Anna C. Need, William Ollier, Aarno Palotie, Antony Payton, Neil Pendleton, Russell A. Poldrack, Katri Räikkönen, Ivar Reinvang, Panos Roussos, Dan Rujescu, Fred W. Sabb, Matthew A. Scult, Olav B Smeland, Nikolaos Smyrnis, John M. Starr, Vidar M. Steen, Nikos C. Stefanis, Richard E Straub, Kjetil Sundet, Aristotle N. Voineskos, Daniel R Weinberger, Elisabeth Widen, Jin Yu, Goncalo Abecasis, Ole A Andreassen, Gerome Breen, Lene Christiansen, Birgit Debrabant, Danielle M Dick, Andreas Heinz, Jens Hjerling-Leffler, M. Arfan Ikram, Kenneth S Kendler, Nicholas G Martin, Sarah E. Medland, Nancy L. Pedersen, Robert Plomin, Tinca J.C. Polderman, Stephan Ripke, Sophie van der Sluis, Patrick F Sullivan, Henning Tiemeier, Scott I. Vrieze, Margaret J Wright, Danielle Posthuma

Posted 06 Sep 2017
bioRxiv DOI: 10.1101/184853 (published DOI: 10.1038/s41588-018-0152-6)

Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer's dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.

Download data

  • Downloaded 5,009 times
  • Download rankings, all-time:
    • Site-wide: 874 out of 100,936
    • In genetics: 64 out of 5,022
  • Year to date:
    • Site-wide: 12,041 out of 100,936
  • Since beginning of last month:
    • Site-wide: 10,455 out of 100,936

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News

  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!