Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.
Seppe GoovaertsHanne HoskensRyan J EllerNoah HerrickAnthony M MusolfCristina M JusticeMeng YuanSahin NaqviMyoung Keun LeeDirk VandermeulenHeather L Szabo-RogersPaul A RomittiSimeon A BoyadjievMary L MarazitaJohn R ShafferMark D ShriverJoanna WysockaSusan WalshSeth M WeinbergPeter D ClaesPublished in: Nature communications (2023)
The cranial vault in humans is highly variable, clinically relevant, and heritable, yet its genetic architecture remains poorly understood. Here, we conduct a joint multi-ancestry and admixed multivariate genome-wide association study on 3D cranial vault shape extracted from magnetic resonance images of 6772 children from the ABCD study cohort yielding 30 genome-wide significant loci. Follow-up analyses indicate that these loci overlap with genomic risk loci for sagittal craniosynostosis, show elevated activity cranial neural crest cells, are enriched for processes related to skeletal development, and are shared with the face and brain. We present supporting evidence of regional localization for several of the identified genes based on expression patterns in the cranial vault bones of E15.5 mice. Overall, our study provides a comprehensive overview of the genetics underlying normal-range cranial vault shape and its relevance for understanding modern human craniofacial diversity and the etiology of congenital malformations.
Keyphrases
- genome wide association study
- genome wide
- magnetic resonance
- dna methylation
- endothelial cells
- copy number
- induced pluripotent stem cells
- young adults
- computed tomography
- white matter
- type diabetes
- gene expression
- induced apoptosis
- transcription factor
- machine learning
- magnetic resonance imaging
- multiple sclerosis
- contrast enhanced
- pluripotent stem cells
- binding protein
- skeletal muscle
- oxidative stress
- adipose tissue
- genome wide association
- drug induced
- convolutional neural network
- genome wide identification
- bioinformatics analysis
- cerebral ischemia