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Genomic architecture of human neuroanatomical diversity

Abstract

Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here, based on our analyses of neuroimaging and whole-genome genotyping data from 1765 subjects, we show that up to 54% of this heritability is captured by large numbers of single-nucleotide polymorphisms of small-effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.

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Acknowledgements

This work was supported by the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology; LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic variations underlying common neuropsychiatric diseases and diseases related to cognitive traits in different human populations; 242257), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (93558), the Swedish Funding Agency FORMAS, the German Bundesministerium und Forschung (FKZ: 01EV0711), Institut Pasteur, CNRS, Université Paris Diderot, the Bettencourt-Schueller Foundation, the Conny-Maeva Foundation, the Orange Foundation, the FondaMental Foundation and the Cognacq-Jay Foundation.

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Correspondence to R Toro.

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Toro, R., Poline, JB., Huguet, G. et al. Genomic architecture of human neuroanatomical diversity. Mol Psychiatry 20, 1011–1016 (2015). https://doi.org/10.1038/mp.2014.99

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