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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
Cerebral cortex (New York, N.Y. 1991), 04/2020, Letnik: 30, Številka: 4Journal Article
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 rG ~ 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 athttps://github.com/neuroanatomy/genomic-architecture.
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