Polygenic Architecture of Human Neuroanatomical Diversity. (28th February 2020)

• Record Type: Journal Article
• Authors: Biton, Anne; Traut, Nicolas; Poline, Jean-Baptiste; Aribisala, Benjamin S; Bastin, Mark E; Bülow, Robin; Cox, Simon R; Deary, Ian J; Fukunaga, Masaki; Grabe, Hans J; Hagenaars, Saskia; Hashimoto, Ryota; Kikuchi, Masataka; Muñoz Maniega, Susana; Nauck, Matthias; Royle, Natalie A; Teumer, Alexander; Valdés Hernández, Maria; Völker, Uwe; Wardlaw, Joanna M; Wittfeld, Katharina; Yamamori, Hidenaga; Bourgeron, Thomas; Toro, Roberto
• Is Part Of: Cerebral cortex. Volume 30:Number 4(2020)
• Page Start: 2307
• Page End: 2320
• Publication Date: 2020-02-28
• Subjects: genetics -- heritability -- neuroimaging -- polygenic architecture -- subcortical structures; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhz241
• Languages: English
• ISSNs: 1047-3211

Abstract

Abstract: 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 <one fourth of the genetic variance. We also observed extensive pleiotropy across regions, with an average genetic correlation of r G ~ 0.45. Genetic correlations were similar to phenotypic and environmental correlations; however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture .