Year: 2023
Type: article
Study design: Observational Study
Abstract: Compelling evidence suggests that human cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein-coding variants impact cognitive function in the adult population (n = 485,930). We identify eight genes (ADGRB2, KDM5B, GIGYF1, ANKRD12, SLC8A1, RC3H2, CACNA1A and BCAS3) that are associated with adult cognitive function through rare coding variants with large effects. Rare genetic architecture for cognitive function partially overlaps with that of neurodevelopmental disorders. In the case of KDM5B we show how the genetic dosage of one of these genes may determine the variability of cognitive, behavioral and molecular traits in mice and humans. We further provide evidence that rare and common variants overlap in association signals and contribute additively to cognitive function. Our study introduces the relevance of rare coding variants for cognitive function and unveils high-impact monogenic contributions to how cognitive function is distributed in the normal adult population.
Source: Nature Genetics
Authors: Chia-Yen Chen, Ruoyu Tian, Tian Ge, Max Lam, Gabriela Sanchez-Andrade, Tarjinder Singh, Lea Urpa, Jimmy Z. Liu, Mark Sanderson, Christine Rowley, Holly Ironfield, Terry Fang, Biogen Biobank Team, The SUPER-Finland study, Aija Kyttälä, Amanda Elliott, Anders Kämpe, Andre Sourander, Annamari Tuulio-Henriksson, Anssi Solismaa, Antti Tanskanen, Ari Ahola-Olli, Arto Mustonen, Arttu Honkasalo, Asko Wegelius, Atiqul Mazumder, Auli Toivola, Benjamin Neale, Elina Hietala, Elmo Saarentaus, Erik Cederlöf, Erkki Isometsä, Heidi Taipale, Imre Västrik, Jaana Suvisaari, Jari Tiihonen, Jarmo Hietala, Johan Ahti, Jonne Lintunen, Jouko Lönnqvist, Juha Veijola, Julia Moghadampour, Jussi Niemi-Pynttäri, Kaisla Lahdensuo, Katja Häkkinen, Katriina Hakakari, Kimmo Suokas, Marjo Taivalantti, Markku Lähteenvuo, Martta Kerkelä, Minna Holm, Nina Lindberg, Noora Ristiluoma, Olli Kampman, Olli Pietiläinen, Risto Kajanne, Sari Lång-Tonteri, Solja Niemelä, Steven E. Hyman, Susanna Rask, Teemu Männynsalo, Tiina Paunio, Tuomas Jukuri, Tuomo Kiiskinen, Tuula Kieseppä, Ville Mäkipelto, Willehard Haaki, Zuzanna Misiewicz, The Northern Finland Intellectual Disability study, Mitja I. Kurki, Jarmo Körkkö, Jukka Moilanen, Outi Kuismin, Mark Daly, Aarno Palotie, Ellen A. Tsai, Hailiang Huang, Matthew E. Hurles, Sebastian S. Gerety, Todd Lencz, Heiko Runz
Institutions: Biogen (United States), Broad Institute, Harvard University, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Northwell Health, Feinstein Institute for Medical Research, Zucker Hillside Hospital, Wellcome Sanger Institute, University of Helsinki, Institute for Molecular Medicine Finland, HiLIFE – Elämäntieteiden Instituutti, GlaxoSmithKline (United States), Finnish Institute for Health and Welfare, University of Turku, Tampere University Hospital, University of Eastern Finland, Niuvanniemi Hospital, Karolinska Institutet, Helsinki University Hospital, University of Oulu, Turku University Hospital, Oulu University Hospital, Hospital District of Helsinki and Uusimaa, Pirkanmaa Hospital District, Hofstra University, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
OpenAlex ID: W4378212201