Polygenic architecture of human neuroanatomical diversity

Biton, A.; Traut, N.; Poline, J.-B.; Aribisala, B. S.; Bastin, M. E.; Bülow, R.; Cox, S. R.; Deary, I. J.; Grabe, H. J.; Hagenaars, S.; Hashimoto, R.; Munoz Maniega, S.; Nauck, M.; Royle, N. A.; Teumer, A.; Valdes Hernandez, M.; Völker, U.; Wardlaw, J. M.; Wittfeld, K.; Alzheimer's Disease Neuroimaging Initiative,; Bourgeron, T.; Toro, R.

doi:10.1101/592337

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bioRxiv · 10.1101/592337

Polygenic architecture of human neuroanatomical diversity

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Abstract

We analysed 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 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 <1/4th 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 at https://github.com/neuroanatomy/genomic-architecture.

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Biton, A., Traut, N., Poline, J.-B., Aribisala, B. S., Bastin, M. E., Bülow, R., Cox, S. R., Deary, I. J., Grabe, H. J., Hagenaars, S., Hashimoto, R., Munoz Maniega, S., Nauck, M., Royle, N. A., Teumer, A., Valdes Hernandez, M., Völker, U., Wardlaw, J. M., Wittfeld, K., Alzheimer's Disease Neuroimaging Initiative,, Bourgeron, T., Toro, R.. 2019-03-28. Polygenic architecture of human neuroanatomical diversity. https://doi.org/10.1101/592337

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