Shared heritability of human face and brain shape

Abstract

Evidence from model organisms and clinical genetics suggests coordination between the developing brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivariate genome-wide association study (GWAS) of cortical surface morphology in 19,644 European-ancestry individuals, identifying 472 genomic loci influencing brain shape, of which 76 are also linked to facial shape. Shared loci include transcription factors involved in craniofacial development, as well as members of signaling pathways implicated in brain-face crosstalk. Brain shape heritability is equivalently enriched near regulatory regions active in either forebrain organoids or facial progenitors. However, we do not detect significant overlap between shared brain-face GWAS signals and variants affecting behavioral-cognitive traits. These results suggest that early in embryogenesis, the face and brain mutually shape each other through both structural effects and paracrine signaling, but this interplay may not impact later brain development associated with cognitive function.

Multivariate genome-wide association study on tissue-sensitive diffusion metrics identifies key molecular pathways for axonal growth, synaptogenesis, and astrocyte-mediated neuroinflammation

“…The CPCs on UKB discovery set found 432, 350, and 273 independent genetic loci associated with N0, ND, and NF, respectively (Figure 1E). The multivariate SNP-heritabilities 15 for N0, ND, and NF are 0.09 (95%CI 0.04 - 0.13), 0.06 (95%CI 0.02 - 0.10), and 0.05 (95%CI 0.01 - 0.09). The discovered loci explained 59%, 60%, and 58% of the SNP-heritabilities for N0, ND, and NF.…”

“…Type 2 Diabetes 49 and puberty timing 50 were also included. Based on a method that tailored for unsigned multivariate statistics 15 , we evaluated the signal shared between two traits using their summary statistics. The amount of shared signals was the Spearman correlation of the average SNP p values within each approximately independent LD blocks.…”

“…As proposed in other multivariate GWAS efforts 15 , we calculated the average for each of the approximately independent LD blocks 56 . Spearman correlations were performed for each pair of the GWAS results.…”

“…We rescaled the χ 2 according the extended methods 15 and then used the stratified LDSC to examine the relative enrichment in the cell-type specific annotations.…”

Association between prenatal alcohol exposure and children’s facial shape. A prospective population-based cohort study

“…Craniofacial development closely corresponds to brain development. 42 Thus, classic facial features of FASD such as short palpebral fissure, smooth philtrum, and thin upper lip have been linked to brain abnormalities and cognitive outcome in FASD and have been used to diagnose children at risk of developing neurobehavioral deflicts. 9,37,38 Low-moderate PAE has also shown adverse associations with children's brain cognitive development, resulting in psychological and behavioral problems.…”