Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence

Philip R. Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E. Savage, Christiaan A. Leeuw, Martijn P. Heuvel, Sophie Sluis and Danielle Posthuma ()
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Philip R. Jansen: Vrije Universiteit Amsterdam
Mats Nagel: Vrije Universiteit Amsterdam
Kyoko Watanabe: Vrije Universiteit Amsterdam
Yongbin Wei: Vrije Universiteit Amsterdam
Jeanne E. Savage: Vrije Universiteit Amsterdam
Christiaan A. Leeuw: Vrije Universiteit Amsterdam
Martijn P. Heuvel: Vrije Universiteit Amsterdam
Sophie Sluis: Vrije Universiteit Amsterdam
Danielle Posthuma: Vrije Universiteit Amsterdam

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The phenotypic correlation between human intelligence and brain volume (BV) is considerable (r ≈ 0.40), and has been shown to be due to shared genetic factors. To further examine specific genetic factors driving this correlation, we present genomic analyses of the genetic overlap between intelligence and BV using genome-wide association study (GWAS) results. First, we conduct a large BV GWAS meta-analysis (N = 47,316 individuals), followed by functional annotation and gene-mapping. We identify 18 genomic loci (14 not previously associated), implicating 343 genes (270 not previously associated) and 18 biological pathways for BV. Second, we use an existing GWAS for intelligence (N = 269,867 individuals), and estimate the genetic correlation (rg) between BV and intelligence to be 0.24. We show that the rg is partly attributable to physical overlap of GWAS hits in 5 genomic loci. We identify 92 shared genes between BV and intelligence, which are mainly involved in signaling pathways regulating cell growth. Out of these 92, we prioritize 32 that are most likely to have functional impact. These results provide information on the genetics of BV and provide biological insight into BV’s shared genetic etiology with intelligence.

Date: 2020
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DOI: 10.1038/s41467-020-19378-5

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