RT Journal Article
SR Electronic
T1 GWAS of brain volume on 54,407 individuals and cross-trait analysis with intelligence identifies shared genomic loci and genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 613489
DO 10.1101/613489
A1 Philip R Jansen
A1 Mats Nagel
A1 Kyoko Watanabe
A1 Yongbin Wei
A1 Jeanne E Savage
A1 Christiaan A de Leeuw
A1 Martijn P van den Heuvel
A1 Sophie van der Sluis
A1 Danielle Posthuma
YR 2019
UL http://biorxiv.org/content/early/2019/04/19/613489.abstract
AB 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 factors1. 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 conducted the largest BV GWAS meta-analysis to date (N=54,407 individuals), followed by functional annotation and gene-mapping. We identified 35 genomic loci (27 novel), implicating 362 genes (346 novel) and 23 biological pathways for BV. Second, we used an existing GWAS for intelligence (N=269,867 individuals2), and estimated the genetic correlation (rg) between BV and intelligence to be 0.23. We show that the rg is driven by physical overlap of GWAS hits in 5 genomic loci. We identified 67 shared genes between BV and intelligence, which are mainly involved in important signaling pathways regulating cell growth. Out of these 67 we prioritized 32 that are most likely to have functional impact. These results provide new information on the genetics of BV and provide biological insight into BV’s shared genetic etiology with intelligence.