Polygenic Architecture of Human Neuroanatomical Diversity

Anne Biton (1, 2) , Nicolas Traut (1) , Jean-Baptiste Poline (3) , Benjamin Aribisala (4, 5, 6) , Mark Bastin (5, 4, 7) , Robin Bülow (8) , Simon R. Cox (4, 5) , Ian J Deary (4, 5) , Masaki Fukunaga (9, 10) , Hans J Grabe (11, 12) , Saskia Hagenaars (4, 5, 13) , Ryota Hashimoto (14) , Masataka Kikuchi (15) , Susana Muñoz Maniega (4, 5, 7) , Matthias Nauck (16, 17) , Natalie A Royle (5, 4, 7) , Alexander Teumer (18) , Maria C Valdés Hernández (5, 4, 7) , Uwe Völker (19, 16) , Joanna Wardlaw (7, 19, 5) , Katharina Wittfeld (12) , Hidenaga Yamamori (15) , Thomas Bourgeron (1) , Roberto Toro (1, 20)

1 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
2 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
3 Department of Neurology and Neurosurgery [Montreal]
4 Centre for Cognitive Ageing and Cognitive Epidemiology
5 University of Edinburgh
6 LASU - Lagos State University
7 BRIC - Brain Research Imaging Center
8 University of Medicine Greifswald
9 National Institute for Physiological Sciences
10 SOKENDAI - Graduate University for Advanced Studies [Hayama]
11 Department of Psychiatry and Psychotherapy
12 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
13 Institute of Psychiatry, Psychology & Neuroscience, King's College London
14 National Center of Neurology and Psychiatry [Tokyo, Japan]
15 Graduate School of Medicine [Osaka]
16 DZHK - German Center for Cardiovascular Research
17 Institute of Clinical Chemistry and Laboratory Medicine
18 Institute for Community Medicine, University Medicine Greifswald, Greifswald
19 Interfaculty Institute of Genetics and Functional Genomics
20 CRI - Centre de Recherches Interdisciplinaires [Paris]

We analyzed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26 000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r ~ 0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (~51%) captured ~1.5 times more genetic variance than the rest, and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF <5% captured

Keywords: genetics; heritability; neuroimaging; polygenic architecture; subcortical structures

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Neurobiology

Anne Biton, Nicolas Traut, Jean-Baptiste Poline, Benjamin Aribisala, Mark Bastin, et al.. Polygenic Architecture of Human Neuroanatomical Diversity. Cerebral Cortex, 2020, 30 (4), pp.2307-2320. ⟨10.1093/cercor/bhz241⟩. ⟨pasteur-02915091⟩